Religion and Environmental Ethics free essay sample

In the paper he wrote Christianity bears a huge burden of guilt and concludes that Hence we shall continue to have a worsening ecologic crisis until we reject the Christian axiom that nature has no reason for existence save to serve man. White depicted Western Christianity as seeing the world existing primarily for the benefit of man, and man, bearing Gods image and sharing in great measure Gods transcendence of nature, exploit nature for his proper ends according to Gods will. This thesis of White shall be referred to as Dominion Hypothesis for ease of identification in this paper. But are the claims in his Dominion Hypothesis valid? Does Christianity bear a burden of guilt for the ecological crisis of the world? The purpose of this paper is to assess the strength of his thesis by firstly analysing what the biblical scriptures and theologians have to say with regard to the relationship of God, man and the environment. We will write a custom essay sample on Religion and Environmental Ethics or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Next the symptoms and origins of our ecological crisis are examined, after which their ties with Western Christianity are assessed to determine whether the later has causal relationship with the former. Finally, after arriving at the conclusion, some recommendations are presented. 1 Whites Thesis Whites thesis can briefly be summarized as: All forms of life modify their contexts, and the human race has in one sense simply done this more than others. However, the human impact on the environment, whilst frequently detrimental in the past, was given an added impetus by Christianity in its Westernized form. Western society, as a product of Westernized Christianity, inherits an exploitative attitude to the natural world which is the key to our present ecological crisis. (Richardson, 1998) . White depicted Western Christianity as seeing the world existing primarily for the benefit of man, and it is according to Gods will that man exploit nature for his proper ends. Biblical verses that align to the Dominion Hypothesis Arguably the following passages from the Bible are aligned to the Dominion Hypothesis and are most frequently cited by ecology critics of the Bible. Then God said, Let us make man in our image, after our likeness; and let them have dominion over the fish of the sea, and over the birds of trhe air, and over the the cattle, and over all the earth, and over every creeping thinng that creeps upon the earth So god created man in his own image, in the image of God he created him; male and female he created them. And God blessed them, and God said to them Be fruitful and multiply, and fill the earth and subdue it; and have dominion over the fish of the sea and over every living thing that moves upon the earth. And God said, Behold, I have given you every plant yielding seed which is upon the face of all the earth, and every tree with seed in its fruit; you shall have them for food. (Gen. 1:26-29) Yet thou has made him little less than God, and dost crown him with glory and honor. Thous hast given him dominion over the works of thy hands; thous hast put all things under his feet; all sheep and oxen, and also the beasts of the field, the birds of the air, and the fish of the sea, whatever passes along the paths of the sea. (Ps. 8:5-8) 2 And God blessed Noah and his sons, and said to them, Be fruitful and multiply, and fill the earth. The fear of you and the dread of you shall be upon every beast of the earth, and upon every bird of the air, upon everything that creeps on the ground and all the fish of the sea; into your hand they are delivered. Every moving thing that lives shall be food for you; and as I gave you the green plants, I give you everything. (Gen. 9:1-3) You have made them to be a kingdom and priests serving our God, and they will reign on earth (Rev. 5:10). According to exegeses by theology scholar (Hiebert, 1996), the term dominion, from the Hebrew verb radah, implies that it grants humans the right and responsibility to rule, to govern the rest of creation. It connotes a hierarchy of power and authority in which the human race is positioned above the rest of the natural world, although the verb radah does not itself define how this dominion is to be exercised, whether benevolently or malevolently. The laws of Leviticus, when they stipulate that household servants are not to be *ruled* harshly (Lev. 25:43, 46, 53), imply that this kind of dominion may be kind and humane. Yet the use of radah in the context of international relations, where it is more commonly employed, carries a decidedly more antagonistic tinge, since it signifies rule over one*s enemies. It occurs frequently in descriptions of military conquest, where it is paired with such verbs as *destroy* (Num. 24:19) and *strike down* (Lev. 26:17; Isa. 14:6). When used of the Israelite king, radah always refers to dominion over his enemies, not to rule over his own Israelite subjects, for which the verb malak, *reign,* is the usual term. Similar conclusions may be drawn about the phrase *subdue the earth* in Gen. :28. The verb *subdue,* from the Hebrew kavash, depicts a hierarchical relationship in which humans are positioned above the earth and are granted power and control over it. The verb kavash is even more forceful than radah, describing the actual act of subjugation, of forcing another into a subordinate position. It is used for military conquest, where the same phrase used in Gen. 1:28 , *subdue the earth/land,* can be employed to depict the destruction and occupation of conquered territory (Num. 32:22, 29). It is also used of the king*s forcing his people into slavery against God*s wishes (Jer. 4:11, 16), and of rape (Esther 7:8; Neh. 5:5). In many of these cases, the abuse {19} of power is patently obvious. 3 Biblical verses that align to the Eco-Friendly perspective On the other hand, the following verses can be interpreted as being aligned to an EcoFriendly view:Let the heavens be glad, and let the earth rejoice; let the sea roar, and all that fills it; let the field exult, and everything in it! Then shall all the trees of the forest sing for joy before the LORD, for he comes, for he comes to judge the earth. He will judge the world in righteousness, and the peoples in his faithfulness. (Psalm 96:11-13) Praise the LORD! Praise the LORD from the heavens; praise him in the heights! Praise him, all his angels; praise him, all his hosts! Praise him, sun and moon, praise him, all you shining stars! Praise him, you highest heavens, and you waters above the heavens! Let them praise the name of the LORD! For he commanded and they were created. And he established them forever and ever; he gave a decree, and it shall not pass away. a Praise the LORD from the earth, you great sea creatures and all deeps, fire and hail, snow and mist, stormy wind fulfilling his word! Mountains and all hills, fruit trees and all cedars! Beasts and all livestock, creeping things and flying birds! Kings of the earth and all peoples, princes and all rulers of the earth! Young men and maidens together, old men and children! Let them praise the name of the LORD, for his name alone is exalted; his majesty is above earth and heaven. (Psalm 148:1-13) *When you besiege a city a long time, to make war against it in order to capture it, you shall not destroy its trees by swinging an axe against them; for you may eat from them, and you shall not cut them down. For is the tree of the field a man, that it should [m]be besieged by you? Only the trees which you known are not fruit trees you shall destroy and cut down, that you may construct siegeworks against the city that is making war with you until it falls. (Deuteronomy 20:19-20) *When you enter the land and plant any kind of fruit tree, regard its fruit as forbidden. For three years you are to consider it forbidden; it must not be eaten. In the fourth year all its fruit will be holy, an offering of praise to the Lord. But in the fifth year you may eat its fruit. In this way your harvest will be increased. I am the Lord your God. (Leviticus 19:2325) You shall not let your cattle breed with a different kind; you shall not sow your field with two kinds of seed; nor shall there come upon you a garment of cloth made of two kinds of stuff. (Leviticus 19:19) For six years you shall sow your land and gather in its yield; but the seventh year you shall let it rest and lie fallow, that the poor of your people may eat; and what they leave the wild beasts may eat. (Exodus 23: 10-11) 5 The nations were angry, and your wrath has come. The time has come for judging the dead, and for rewarding your servants the prophets and your people who revere your name, both great and small * and for destroying those who destroy the earth. * (Rev 11:18) For true and righteous are his judgments: for he hath judged the great whore, which did corrupt the earth with her fornication, and hath avenged the blood of his servants at her hand. (Rev 19:2) They will neither harm nor destroy on all my holy mountain, for the earth will be filled with the knowledge of the Lord as the waters cover the sea. (Isaiah 11:9) The wolf and the lamb will feed together, and the lion will eat straw like the ox, but dust will be the serpents food. They will neither harm nor destroy on all my holy mountain, says the LORD. (Isaiah 65:25) Theology scholars commenting on this view of nature of the Old Testament wrote : It is therefore fair to conclude that nature is far from de-animated in Biblical thought. (Wybrow, 1990), The natural world may not be see n as sacred or divine in the Bible, but it is certainly not dead, lifeless, and outside the divine moral framework here are no scriptures suggesting that nature was viewed as dead matter to be manipulated by man.. (Kinsley, 1995). Referring to the theme of the kingdom of God running through the New Testament, Zerbe (1992) argues that the New Testament has significant ecological implications, he explained: Isaiah*s vision of restored humanity and nature climaxes with the statement that there will no longer be any hurt or destruction in creation (Isa. 11:9; 65:25). And John*s vision of judgment states that those who destroy the earth will themselves be destroyed (Rev. 11:18; 19:2). It is noteworthy that the prophetic critique of Rome in Rev. 17:1-19:4 closely connects greed and the earth*s destruction: the insatiable desire for consumption and wealth is what results in the destruction of people and the earth. The corresponding passages are as quoted above. 6 Alternative view: Dominion Theology in Genesis 1 vs. Dependence Theology in Genesis 2 And lastly, but most importantly, consider the following two verses, both from Genesis 2:Then the Lord God formed a man from the dust of the ground and breathed into his nostrils the breath of life, and the man became a living being. (Genesis 2:7) The Lord God took the man and put him in the Garden of Eden to work it and take care of it. (Genesis 2:15) What is very important to the discussion in this paper is that according to Hiebert (1996), as evident in the above verses, Genesis 2 presents an alternative to the dominion theology of Genesis 1, which he calls dependence theology. His thesis being that the first human is made of the same arable soil as are all of other forms of life; and the divine breath into which his nostrils blown is the same with which all the animals live and breathe (Gen. :7; 7:22). The role of the human in the earth described is not that of mastery but of servanthood. In this account of creation, the theology of the human place in creation is not a theology of dominion but a theology of dependence (Hiebert, 1996). This theology is evident in other parts of Scripture, examples including Psalm 104 and the Book of Job (McKibben,1994). According to Hiebert: In this tradition (Genesis 2), the human being is positioned very differently within the world of nature. Here the archetypal human is made not in the image of God but out of topsoil, out of the arable land that was cultivated by Israelite farmers (Gen. 2:7). As a result of this kind of creation, humans hold no distinctive position among living beings, since plants and animals also were produced from this same arable soil (2:9, 19). Moreover, the role assigned humans within creation in this story is not to rule (radah) and to subdue (kavash) but rather to {23} *serve* (avad; Gen. 2:15; 3:23). The Hebrew term avad is properly translated *till* in these verses (NRSV), since it clearly refers to the cultivation of arable land. But avad is in fact the ordinary Hebrew verb *serve,* used of slaves serving masters and of humans serving God (Gen. 12:16; Exod. 4:23). , the conflicts of Genesis I and Genesis 2 notwithstanding, there are lots of thesis arguing that there is no inconsistency between the two chapters and the ouvert differences are due to different ways in recapitulation only . (Young, 1960),(Archer, 1964),(Kitchen,1966) On another plane of our discussion, we shall now turn to a brief discussion of the historical origins of our ecological crisis. 7 The Historical Origins of our Ecological Crisis There is general consensus that the planet earth is heading towards environmental catastrophe due to alarming development at different fronts: the green house effect, acid rain, damage to ozone layer, deforestation, loss of biodiversity, chemical pollution, freshwater shortage, etc. , amongst others. (Magdoff Foster, 2011).. But how did all these pollutions started? according to Thorsheim (2006), in his book The Invention of Pollution, it all started with the use of fossil energy, which was conducive to the Industrial Revolution. The first largescale commercial use of fossil energy was coal in Britain in the 1800s, which he referred to as a Faustian bargain for Britain, since on the one hand it helped to bring tremendous wealth, advance and power to the country, whilst on the other coal also filled the air with immense smoke and acidic vapors, which was one of the origins of what we now call the green house effect and acid rain. Fossil oil as energy had also been popularized ever since Edwin L. Drake drilled the first oil well in 1853, but the impact on the environment is equally as detrimental as Coal, if not more so. The fossil energy application was conducive to the Industrial Revolution, and the Industrial Revolution had led to the advance in comfort, convenience and enjoyment, from dwelling comfort to transport convenience to material needs, leading to the abundance and later overabundance in supply of products. Consumerism in the past decades had eventually been invented in order to help us to recognize our needs, and due to the needs for growth of enterprises, some products have also began to be designed with built-in obsolescence. All these initiatives had contributed to the generation of ever more wastes than in the centuries before the industrial revolution, much more than can be sinked by the earth, which contributed to the chemical pollution of soil, water, which has also altered the bio-diversity of the Earth. 8 Ever since the Industrial Revolution, the consumption of energy has experienced exponential growth (see figure 1. 1). Concomitantly, different kind of detrimental impacts had been inflicted upon the ecology of the earth (see figure 1. 2). As an in-depth analysis of our ecological crisis is out of the scope of this paper, focus is now centred on the origin of the crisis, viz. the advent of fossil energy application, which shall be discussed below. Some key developments relating to fossil energy application:1665 Invention of the first modern industrial steam engine by English inventor Edward Somerset which can use wood or coal as fuel 1794 First produce of Coal Gas by William Murdoch 1853 First refinement of Kerosene by Abraham Gesner 1859 Drilling of first Oil Well by Edwin Drake 1859 Building of the first practical self-combustion engine by Etienne Lenoir Religious Background of the Inventors / Innovators Astonishingly, what the above key developments have in common, according to research by the author, is that all the inventors / innovators were Judeao-Christian in religious belief, as can be listed below according to extant data. Inventor/Innovator Place of Birth Religion Edward Somerset (1601-67) Monmouthshire, Bri tain Roman Catholic William Murdoch (1754 1839) Cumnock, Scotland Roman Catholic Abraham Gesner (1797-1864) Nova Scotia, Canada Protestant Christian Edwin Drake (1819-1880) New York, U. S. A. Jewish Jean-Joseph-Etienne Lenoir (1822-1900) Mussy-la-Ville, Belgium Roman Catholic However, just as one cannot say that the inventions or innovations in fossil energy application has been due to Western Christianity, as otherwise one will fall into the post-hoc ergo procter hoc fallacy, it is likewise not valid to attribute the ecological crisis directly to Western Christianity. However, If we put the question conversely by asking that if the inventors/innovators were pantheistic, believing that the nature is sacred in itself and should be reverred, then it is highly unlikely that the inventions/innnovations had been conjured and accomplished by them. Science and Christianity It has been argued that science and christianity are coherent to each other, A British Scientist, Robert Clark, once said we may interpret the fact scientific development has only occurred in a Christian culture. The ancients had brains as good as ours. In all civilizations, Babylonia, Egypt, Greece, India, Rome, Persia, China and so on, science developed to a certain point and then stopped. It is easy to argue speculatively that science might have been able to develop in the absence of Christianity, but in fact, it never did. And no wonder. For the non*Christian world felt there was something ethically wrong about science. In Greece, this conviction was enshrined in the legend of Prometheus, the fire*bearer and prototype scientist who stole fire from heaven thus incurring the wrath of the Gods. 10 Consider also these statements from renowned scientists; William Thomson: Do not be afraid to be free thinkers. If you think strongly enough, you will be forced by science to the belief in God. Isaac Newton: This most beautiful system of the sun, planets and comets could only proceed from the counsel and dominion of an intelligent and powerful Being , Stephen Hawking:In fact, if one considers the possible constants and laws that could have emerged, the odds against a universe that produced life like ours are immense. Conclusion This paper has attempted to examine the hypothesis of Lynn Whites that Christianity bears significant responsibility for the earths ecological crisis. The author has attempted to typologize and quote verses from the scriptures, exegeses and writings of theologians on the Biblical scriptures depicting the relationship of God, man and nature. Whilst according to the Dominion theological perspective as discussed above, the hierarchal relationship of God-gt;Man-gt;Nature (see figure 1. 3) is apparent, in the Dependence theological perspective, the hierarchal relationship of God-gt;Man ; God -gt; Nature (see figure 1. 4) is also evident. God God Man Man Nature Nature Figure 1. 3 The Dominion Perspective Figure 1. 4 The Dependence Perspective Other verses as listed under the section Passages that echo Eco-Friendly also act as a counter-argument for the Dominion hypothesis. It would seem therefore that Whites hypothesis that Western Christianity sees the world existing primarily for the benefit of man and therefore Christianity bears a huge burden of guilt is not grounded solidly, because as mentioned above, there are many verses which encourage man to be benign to our environment, and conversely, there is no single passage asking man to abuse nature for his primarily benefit only. However, if White argued that Christians bears a burden of guilt, then it is less reputable, as explained in the next paragraph. 11 If one concurs that scientific thinking is coherent to Christian belief, as discussed above, and like White argues in his paper, Western Christianity has been contributory in promoting modern science and technological advance, and from the standpoint of the analysing of advent of fossil energy as the origin of our ecological crisis, which does have tremendous detrimental impacts to our environment, it seems evident that Christians do have a direct linkage to the inventions and innovations leading to the mass scale use of fossil energy, the detrimental origin to our ecological system. Recommendations It can be said that with subtlety in the Biblical scriptures, interpretations are often contingent upon the context and the wisdom of the readers, as inspired at different times. What can be said is that given the state of development before the advent of sciences, man had been under the perpetual threats of nature, from attacks by animals, storms, sickness to famines and other disasters. The Dominion theological perspective no doubt inspired man to develop creative thinking about mastering the nature for the betterment of his lifelihood and survival, lacking which man might still be living rather primitively. The advent of sciences and most notably the Industrial Revolution can be depicted as the epitome of this mentality. As our civilization, technology and wisdom progresses, we should now be in a position to recognize that a Dominion mentality to the nature is detrimental to our environment and it is time that we revisit the scriptures to investigate whether we have overlooked an alternative theology in the Bible for seeing our relationship with nature-the Dependence approach, treating the nature as equals of ours, in which we serve god to ensure its goodness, and ensuring its long term sustainability to prepare for the Kingdom of God. 2 Bibliography Lynne White Jr (1967), The Historical Roots of Our Ecological Crisis, reproduced in John Barr (ed), The Environmental Handbook (London: Ballantine/Friends of the Earth, 1971) pp 3-16. David Kinsley, Ecology and Religion: Ecological Spirituality in Cross-Cultural Perspective (Englewood Cliffs, N. J. : Prentice Hall, 1995) Richard Cameron Wyb row The Bible, Baconism, and Mastery over Nature: The Old Testament and Its Moderrn Misreading (Ph. D disserrtation, McMaster University, Hamillton Ont. Canada, 1990) p. 206 Theodore Hiebert, Professor of Old Testament at McCormick Theological Seminary, Chicago, Illinois. , Direction (Winnipeg, MB), 1996 Gordon Zerbe, Assistant Professor of New Testament at Canadian Mennonite Bible College, Winnipeg, Manitoba. , Direction (Winnipeg, MB), 1992 Howard Snyder, Liberating the Church: The Ecology of Church and Kingdom (Downers Grove: Inter-Varsity Press, 1983) 45-51. Young, Edward J. (1960) An Introduction to the Old Testament (Grand Rapids: Eerdmans Publishing Co. ). Archer, Gleason (1964), A Survey of Old Testament Introduction (Chicago: Moody Press). Kitchen, Kenneth (1966), Ancient Orient and Old Testament (London: Tyndale Press). Thorsheim, Peter (2006), Inventing Pollution: Coal, Smoke and Culture in Britain since 1800 13

Ion Channel Disease Essays

Ion Channel Disease Essays Ion Channel Disease Essay Ion Channel Disease Essay MECH A NIS MS OF D IS EASE Review Article Mechanisms of Disease F R A N K L I N H . E P S T E I N , M. D. , Editor ION CHANNELS - BASIC SCIENCE AND CLINICAL DISEASE AND MICHAEL J. ACKERMAN, M. D. , PH. D. , DAVID E. CLAPHAM, M. D. , PH. D. I ON channels constitute a class of proteins that is ultimately responsible for generating and orchestrating the electrical signals passing through the thinking brain, the beating heart, and the contracting muscle. Using the methods of molecular biology and patch-clamp electrophysiology, investigators have recently cloned, expressed, and characterized the genes encoding many of these proteins. Ion-channel proteins are under intense scrutiny in an effort to determine their roles in pathophysiology and as potential targets for drugs. Defective ion-channel proteins are responsible for cystic fibrosis,1 the long-QT syndrome,2 heritable hypertension (Liddle’s syndrome),3,4 familial persistent hyperinsulinemic hypoglycemia of infancy,5,6 hereditary nephrolithiasis (Dent’s disease), and a variety of hereditary myopathies,7-9 including generalized myotonia (Becker’s disease), myotonia congenita (Thomsen’s disease), periodic paralyses, malignant hyperthermia, and central core storage disease (Table 1). Elucidating the mechanisms of these diseases will benefit medicine as a whole, not just patients with a particular disease. For instance, although the inherited long-QT syndrome is not common, identifying the underlying defects in the KVLQT1 and HERG potassium channels and the SCN5A sodium channels may benefit the study of ventricular arrhythmias, which are responsible for 50,000 sudden deaths each year in the United States. Likewise, al- hough a defect in the recently cloned epithelial sodium channel (ENaC) is the basis of a very rare form of inherited hypertension (Liddle’s syndrome, or pseudoaldosteronism), normal ENaC may serve as an alternative target in attempts to correct the physiologic defects created by the cystic fibrosis transmembrane regulator (CFTR), which is mutated in patients with cystic fibrosis, and work with ENaC may provide insight into the mechanism of essential hypertension. This review focuses on ion channels as functioning physiologic proteins, sources of disease, and targets for therapy. We will discuss two prominent diseases caused by defects in ion-channel proteins, as well as two specific ion channels whose recent molecular identification raises new prospects for pharmacologic manipulation. PHYSIOLOGY OF ION CHANNELS From the Department of Pediatrics and Adolescent Medicine, Mayo Foundation, Rochester, Minn. (M. J. A. ); and the Department of Cardiology, Children’s Hospital Medical Center, Department of Neurobiology, Harvard Medical School, Boston (D. E. C. ). Address reprint requests to Dr. Ackerman at the Department of Pediatrics and Adolescent Medicine, Mayo Eugenio Litta Children’s Hospital, Mayo Foundation, Rochester, MN 55905.  ©1997, Massachusetts Medical Society. Ion channels are macromolecular protein tunnels that span the lipid bilayer of the cell membrane. Approximately 30 percent of the energy expended by cells is used to maintain the gradient of sodium and potassium ions across the cell membrane. Ion channels use this stored energy much as a switch releases the electrical energy of a battery. They are more efficient than enzymes; small conformational changes change (gate) a single channel from closed to open, allowing up to 10 million ions to flow into or out of the cell each second. A few picoamps (10 12 A) of current are generated by the flow of highly selected ions each time the channel opens. Since ion channels are efficient, their numbers per cell are relatively low; a few thousand of a given type are usually sufficient. Ion channels are usually classified according to the type of ion they allow to pass - sodium, potassium, calcium, or chloride - although some are less selective. They may be gated by extracellular ligands, changes in transmembrane voltage, or intracellular second messengers. Conductance is a measure of the ease with which ions flow through a material and is expressed as the charge per second per volt. The conductance of a single channel, g, as distinguished from the membrane conductance (G) of all the channels in the cell, is defined as the ratio of the amplitude of current in a single channel (i ) to the electromotive force, or voltage (V): g i . V The direction in which ions move through a channel is governed by electrical and chemical concentraVol ume 336 Numbe r 22 575 The New Engla nd Journa l of Medicine TABLE 1. HERITABLE DISEASES MODE OF INHERITANCE* OF ION CHANNELS. NO. OF AMINO ACIDS DISEASE ION-CHANNEL GENE (TYPE) CHROMOSOME LOCATION COMMON MUTATIONS†  Cystic fibrosis Familial persistent hyperinsulinemic hypoglycemia of infancy Hypercalciuric nephrolithiasis (Dent’s disease) Liddle’s syndrome (hereditary hyperten sion; pseudoaldosteronism) AR AR X-linked CFTR (epithelial chloride channel) SUR1 (subunit of ATP-sensitive pancreatic potassium channel) CLCN5 (renal chloride channel) 7q 11p15. 1 Xp11. 22 480 1582 746 AR ENaC (epithelial sodium channel) a subunit b subunit g subunit 12p 16p 16p 1420 640 649 F508 (70 percent of cases) and 450 other defined mutations Truncation of NBD2 (nucleotidebinding domain 2) 1 intragenic deletion, 3 nonsense, 4 missense, 2 donor slice, 1 microdeletion R564stop, P616L, Y618H (all in b subunit); premature stop codon in b and g subunits; C-terminal truncation Long-QT syndrome (cardiac arrhythmia) LQT1 LQT2 LQT3 Myopathies Becker’s generalized myotonia Central core storage disease Congenital myasthenic syndrome AD KVLQT1 (cardiac potassium channel) HERG (cardiac potassium channel) SCN5A (cardiac sodium channel) 11p15. 5 7q35–36 3p21–24 581 1159 2016 1 intragenic deletion, 10 missense 2 intragenic deletions, 5 missense KPQ1505–1507, N1325S, R1644H D136G, F413C, R496S R163C, I403M, Y522S, R2434H T264P L269F , G153S T698M, T704M, M1585V, M1592V R528H, R1239H G341R, G2433R G1306A Q552R V1293I, G1306V, T1313M, L1433R, R1448C, R1448H, V1589M S804F, G1306A, G1306E, I1160V D136G, G230E, I290M, P480L AR ? ? Hyperkalemic periodic paralysis Hypokalemic periodic paralysis Malignant yperthermia Masseter-muscle rigidity (succinylcholine-induced) Myotonia levior Paramyotonia congenita Pure myotonias (fluctuations, permanins, acetazolamideresponsive) Thomsen’s myotonia congenita AD AD AD ? AD AD AD AD CLCN1 (skeletal-muscle chloride channel) RYR1 (ryanodine calcium channel) nAChR (nicotinic acetylcholine receptor) e subunit a subunit (slow channel) SCN4A (skeletal-muscle sodium channel) CACNL1A3 (dihydropine-sensitive calcium channel) RYR1 SCN4A CLCN1 SCN4A SCN4A CLCN1 7q35 19q13. 1 17p 2q 17q23–25 1q31–32 19q13. 1 17q23–25 7q35 17q23–25 17q23–25 7q35 988 5032 473 457 1836 1873 5032 1836 988 1836 1836 988 AR denotes autosomal recessive, and AD autosomal dominant. † Missense mutations are represented by the standard nomenclature (AxxxB, meaning that at amino acid position xxx, amino acid A has been replaced by amino acid B). tion gradients. Ions flow passively through ion channels down a chemical gradient. Electrically charged ions also move in an electrical field, just as ions in solution flow to one of the poles of a battery connected to the solution. The point at which the chemical driving force and the electrical driving force are exactly balanced is called the Nernst potential (or reversal potential [Erev]). Above or below this point of equilibrium, a particular species of ion flows in the direction of the dominant force. The net flow of electricity across a cell membrane is predictable given the concentrations of ions and the number, conductances, selectivities, and gating properties of the various ion channels. Electrophysiologic concepts are simplified by recalling the Nernst potentials of the four major ions 1576 May 2 9 , 1 9 9 7 across the plasma membrane of cells. These are approximated as follows: sodium, 70 mV; potassium, 98 mV; calcium, 150 mV; and chloride, 30 to 65 mV (Fig. 1). The positive and negative signs reflect the intracellular potential relative to a ground reference electrode. When only one type of ion channel opens, it drives the membrane potential of the entire cell toward the Nernst potential of that channel. Thus, if a single sodium-selective channel opens in a cell in which all other types of channels are closed, the transmembrane potential of the cell will become ENa ( 70 mV). If a single potassium channel opens, the cell’s transmembrane potential will become EK ( 98 mV). Because cells have an abundance of open potassium channels, most cells’ transmembrane potentials (at rest) are approximately MEC H A NIS MS OF D IS EASE Extracellular Cell membrane Intracellular Ca2 Ion channels 2. 5 mM Depolarization 0. 0001 mM Nernst potential (Erev) 150 mV Control mechanisms 142 mM Depolarization 10 mM Na 70 mV Gating Voltage Time Direct agonist G protein Calcium Depolarization Nonselective Repolarization 0 mV Modulation Increases in phosphorylation   Oxidation–reduction Cytoskeleton Calcium ATP 101 mM Repolarization Cl Depolarization 5–30 mM Cl 30 to 65 mV 4 mM Repolarization 155 mM K 98 mV Figure 1. Physiology of Ion Channels. Five major types of ion channels determine the transmembrane potential of a cell. The concentrations of the primary species of ions (sodium, calcium, chloride, and potassium) are millimolar. The ionic gradients across the membrane establish the Nernst potentials of the ion-selective channels (approximate values are shown). Under physiologic conditions, calcium and sodium ions flow into the cells and depolarize the membrane potential (that is, they drive the potential toward the values shown for ECa and ENa), whereas potassium ions flow outward to repolarize the cell toward EK. Nonselective channels and chloride channels drive the potential to intermediate voltages (0 mV and 30 to 65 mV, respectively). 0 mV, near EK. When more than one type of ion channel opens, each type â€Å"pulls† the transmembrane potential of the cell toward the Nernst potential of that channel. The overall transmembrane potential at a given moment is therefore determined by which channels are open and which are closed, and by the strength and numbers of the channels. A cell with one o pen sodium channel and one open potassium channel, each with the same conductance, will have a transmembrane potential halfway between ENa ( 70 mV) and EK ( 98 mV), or 14 mV. The result is the same when there are 1000 equal-conductance, open sodium and potassium channels. Ion channels are both potent and fast, and they are tightly controlled by the gating mechanisms of the cell (Fig. 1). The modern way to see an ion channel in action is to use the patch-clamp technique. With this method,10 a pipette containing a small electrode is pressed against the cell membrane so that there is a tight seal between the pipette and the membrane (Fig. 2). In essence, the electrode isolates and captures all the ions flowing through the 1 to 3 mm2 of membrane that is defined by the circular border of the pipette. In this fashion, the ionic current passing through a single ion channel can be collected and measured. Several geometric configurations can be used if a mechanically stable seal is formed. The current passing through the attached patch (cell-attached configuration), a detached patch (inside-out or outside-out configuration), or the whole cell can be measured, providing information about ion channels within the Vol ume 336 Numbe r 22 1577 The New Engla nd Journa l of Medicine A Cellattached mode B Electrode Pipette Insideout mode C Wholecell mode Acetylcholine Acetylcholine Cell membrane IK. ACh g 40 pS to 1 msec Closed pA Closed Gbg protein pA msec Open Open msec msec Figure 2. Patch. In the â€Å"cell-attached† mode (Panel A), a pipette is pressed tightly against the cell membrane, suction is applied, and a tight seal is formed between the pipette and the membrane. The seal ensures that the pipette captures the current flowing through the channel. In the cell-attached membrane patch, the intracellular contents remain undisturbed. Here, acetylcholine in the pipette activates the IK. ACh, which has a characteristic open time (tO) of 1 msec and a conductance (g) of 40 picosiemens. In the inside-out mode (Panel B), after a cell-attached patch has been formed, the pipette is pulled away from the cell, ripping off a patch of membrane that forms an enclosed vesicle. The brief exposure to air disrupts only the free hemisphere of the membrane, leaving the formerly intracellular surface of the membrane exposed to the bath. Now the milieu of the intracellular surface of the channels can be altered. In this figure, adding purified Gbg protein to the exposed cytoplasmic surface activates the IK. ACh. In the whole-cell mode (Panel C), after a cell-attached patch has been formed, a pulse of suction disrupts the membrane circumscribed by the pipette, making the entire intracellular space accessible to the pipette. Instead of disrupting the patch by suction, a pore-forming molecule, such as amphotericin B or nystatin, can be incorporated into the intact patch, allowing ions access to the interior of the cell but maintaining a barrier to larger molecules. In this figure, the net current (IK. ACh) after the application of acetylcholine is shown. environment of the cell, in isolation from the rest of the cell, or over the entire cell, respectively. MOLECULAR BLUEPRINTS OF ION CHANNELS Many ion channels have been cloned by assaying their function directly with the use of oocytes from South African clawed toads (Xenopus laevis). 11 These oocytes are large enough to be injected with exogenous messenger RNA (mRNA) and are capable of synthesizing the resulting foreign proteins. In â€Å"expression cloning,† in vitro transcripts of mRNA from a complementary DNA (cDNA) library derived from a tissue known to be rich in a particular ion channel are injected into individual oocytes. Subsequently, the currents in the oocytes are meas1578 May 2 9 , 1 9 9 7 ured by two-electrode voltage clamp techniques. The cDNA library is serially subdivided until injected mRNA from a single cDNA clone is isolated that confers the desired ion-channel activity. Moreover, mutant cDNA clones with engineered alterations in the primary structure of the protein can be expressed and the properties of the ion channel can be studied to determine which regions of the protein are critical for channel activation and inactivation, ion permeation, or drug interaction. Most ion-channel proteins are composed of individual subunits or groups of subunits, with each subunit containing six hydrophobic transmembrane regions, S1 through S6 (Fig. 3A). 13 The sodium and calcium channels comprise a single (a) subunit containing four repeats of the six transmembrane-span- A M ECH A NIS MS OF D IS EASE A C-type slow inactivation B K Extracellular S4 S1 S2 S3 S4 S5 H5 S6 S4 S4 S4 Cell membrane †Ball and chain† N-type fast inactivation P N S4 voltage sensor H5 channel pore C K Intracellular P P K Figure 3. Structure of Ion Channels. Panel A shows a subunit containing six transmembrane-spanning motifs, S1 through S6, that forms the core structure of sodium, calcium, and potassium channels. The â€Å"ball and chain† structure at the N-terminal of the protein is the region that participates in N-type â€Å"fast inactivation,† occluding the permeation pathway. The circles containing plus signs in S4, the voltage sensor, are positively charged lysine and arginine residues. Key residues lining the channel pore (H5) are found between S5 and S6. The genes for sodium and calcium channels encode a protein containing four repeats of this basic subunit, whereas the genes for voltageactivated potassium channels (Kv) encode a protein with only a single subunit. The genes for Kir channels encode a simple subunit structure containing only an H5 (pore) loop between two transmembrane-spanning segments. P denotes phosphorylation. Panel B shows four such subunits assembled to form a potassium channel. Although no mammalian voltage-dependent ion-channel structure has been revealed at high resolution by x-ray crystallography, the dimensions of the pore region shown here were derived by using high-affinity scorpion toxins and their structures (as determined by nuclear magnetic resonance imaging) as molecular calipers. 12 The pore region appears to have wide intracellular and extracellular vestibules (approximately 2. 8 to 3. 4 nm wide and 0. 4 to 0. 8 nm deep) that lead to a constricted pore 0. 9 to 1. 4 nm in diameter at its entrance, tapering to a diameter of 0. 4 to 0. 5 nm at a depth of 0. 5 to 0. nm from the vestibule. ning motifs. Voltage-gated potassium channels (Kv; this nomenclature refers to K channel, voltagedependent) are composed of four separate subunits, each containing a single six-transmembrane–spanning motif (Fig. 3B). 14 The subunits are assembled to form the central pore in a process that also determines the basic properties of gating and permeation charact eristic of the channel type. The peptide chain (H5 or P loop) between the membrane-spanning segments S5 and S6 projects into and lines the water-filled channel pore. Mutations in this region alter the permeation properties of the channel. S4 contains a cluster of positively charged amino acids (lysines and arginines) and is the major voltage sensor of the ion channel. Voltage-dependent â€Å"fast inactivation† of the channel is mediated by a tethered amino-terminal– blocking particle (the â€Å"ball and chain†) that swings in to occlude the permeation pathway. 15 The most recently discovered family of ion-channel proteins is that containing the inwardly rectifying potassium-selective channels (Kir, for K channel, inward rectifier). These channels determine the transmembrane potential of most cells at rest, because hey are open in the steady state. Kir channels are known as inward rectifiers because they conduct current much more effectively into the cell than out of it. Despite this biophysical property of the Kir channels, the physiologically important current is the outward one that accompanies the efflux of potassium ions. The topography of Kir channels resembles that of Kv channels, but the su bunits in Kir channels lack the S1 to S4 segments present in Kv channels. 16 With only two transmembrane-spanning segments, Kir channels have a deceptively simple domain surrounding the conserved H5 pore. However, pore formation by different combinations of subunits, direct gating of G proteins, and interactions with other proteins adds considerable complexity to the behavior of the Kir channels. HERITABLE DISEASES ASSOCIATED WITH ION-CHANNEL MUTATIONS Cystic Fibrosis One in 27 white persons carries a mutant CFTR gene, and 1 in 2500 to 3000 is born with cystic fiVol ume 336 Numbe r 22 1579 The New Engla nd Journa l of Medicine A B Cell membrane TM1 TM6 TM7 Extracellular TM12 Skin Cl , 60 mmol/liter Lungs Bronchiectasis Pneumothorax Hemoptysis Cor pulmonale N F508 NBD1 ATP ADP Pi NBD2 ATP ADP Pi Liver Obstructive biliary tract disease Pancreas Enzyme insufficiency Insulin-dependent diabetes mellitus Regulatory domain S I P Reproductive tract Male infertility Congenital absence of vas deferens PKA PP2A C 1 Gene therapy to replace CFTR gene (phase 1) Extracellular Cell membrane 3 Activate mutant CFTR with NS004 (experimental) 2 Direct CFTRprotein delivery (in vitro) 5 Activate non-CFTR chloride channels with aerosolized UTP (phase 3) 6 Decrease sodium uptake by blocking ENaC with aerosolized amiloride (phase 3) Na CFTR P2R R P lCI. ATP Cl P Intracellular I Meconium ileus S Small intestine P ENaC P ATP Intracellular Cl 4 Chaperonins (none tested yet) 1580 May 2 9 , 1 9 9 7 P S I P Endoplasmic reticulum S I P S I P P M EC H A NIS MS OF D IS EASE Figure 4. Cystic Fibrosis and CFTR. In cystic fibrosis, defective apically located membrane chloride channels (CFTR) in a variety of epithelial cells do not allow the egress of chloride ions into the lumen. Control over epithelial sodium channels is also lost, increasing the reabsorption of sodium from the lumen. Thick, desiccated mucus results, which accounts for the primary clinical manifestations of the disease (Panel A). 7 CFTR contains 12 transmembrane segments (TM1 through TM12, Panel B), several of which (TM1, TM6, and TM12) contribute to the chloride-channel pore. There are also two nucleotide-binding domains (NBD1 and NBD2) and a regulatory domain. The chloride channel is regulated by ATP binding and hydrolysis at the nucleotide-binding domains and by the phosphorylation (P) of serine residues (S) in the regulatory domain. The most common mutation in cystic fibrosis, found in more than 70 percent of cases, involves a deletion of a single amino acid (phenylalanine) in NBD1 ( F508). PKA denotes protein kinase A, PP2A protein phosphatase 2A, and Pi inorganic phosphorus. Molecular strategies to treat cystic fibrosis (Panel C) include replacing the mutant chloride channel by gene therapy (1) or protein delivery (2); improving the secretion from the existing mutant CFTR protein with CFTR-channel openers, such as NS004 (3) or â€Å"chaperonins† for F508 in the endoplasmic reticulum (4); bypassing the CFTR defect by activating other chloride channels with aerosolized uridine triphosphate (UTP) (5); and blocking the increased reabsorption of sodium through epithelial sodium channels (ENaC) with aerosolized amiloride (6). The investigational stages of these strategies are given in parentheses. P2R denotes type-2 purinergic receptor, and R regulatory domain. brosis (among blacks the incidence is 1 in 14,000, and among Asians it is 1 in 90,000). The manifestations of cystic fibrosis stem from a defect in a chloride-channel protein, CFTR, that does not allow chloride to cross the cell membrane (Fig. 4A). 7 The CFTR gene encodes a chloride channel that is activated by the binding of ATP to its nucleotide-binding domains and by the phosphorylation of key serine residues in its regulatory domain; the phosphorylation is mediated by cyclic AMP and protein kinase A (Fig. 4B). 18-21 CFTR also appears to regulate the absorption of sodium through ENaC, the epithelial sodium channel, and to activate other â€Å"outwardly rectifying† chloride channels. More than 450 mutations have been identified in CFTR, which contains 1480 amino acids. A deletion of phenylalanine at position 508 ( F508) accounts for more than 70 percent of cases of cystic fibrosis and is associated with severe pancreatic insufficiency and pulmonary disease. The F508 CFTR channel conducts chloride reasonably well when it is incorporated into a cell membrane, but because of improper folding the mutant protein becomes stuck in intracellular organelles and is not inserted into the cell membrane. 2 The majority of mutant CFTR proteins are processed abnormally, like the F508 mutant, but some mutations cause either defects in regulation or defective conduction through the CFTR channel. 23 Different CFTR genotypes may provide opportunities to develop unique therapeutic strategies. For instance, misfolded mutants could be escorted to the membrane by yet-to-be-invented â€Å"chaperonins,† whereas the action of poorly conducting mutant proteins may be enhanced by CFT R-specific channel openers. Molecular genotypes are correlated with the severity of pancreatic insufficiency, but not with the severity of pulmonary disease. 24 An exception is the A455E CFTR mutant (in which alanine is changed to glutamic acid at position 455), which has been associated with mild lung disease and accounts for 3 per- cent of cases of cystic fibrosis in the Netherlands. 25 In addition, a primarily genital phenotype of cystic fibrosis that involves the congenital bilateral absence of the vas deferens has been described in otherwise healthy males who are heterozygous for the F508 CFTR mutation. 6 Pulmonary disease accounts for over 90 percent of mortality from cystic fibrosis, and therefore treatment is mostly directed at ameliorating lung disease. Therapy includes antibiotics to eliminate common respiratory pathogens (Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, and Staphylococcus aureus), recombinant human DNase to decrease the viscosity of secretions, and antiinfl ammatory drugs to reduce the inflammatory response. 7 The recognition of the ion-channel defect in cystic fibrosis has led to novel approaches, such as replacing the defective channel gene by gene transfer with either viral carriers such as adeno-associated virus or nonviral carriers such as cationic liposomes (now in phase 1 trials)28; stimulating the activation of reduced numbers of functional ion channels with a CFTR-channel opener (NS004, a substituted benzimidazolone)29; mobilizing mutant CFTR proteins to the cell surface30,31; counteracting the defect in chloride efflux by blocking the influx of sodium with amiloride32,33; and bypassing CFTR-mediated conductance of chloride by activating other chloride channels, such as ICl. Swell, ICl. Ca, and ICl. ATP34 (Fig. 4C). Long-QT Syndrome A more detailed understanding of cardiac arrhythmogenesis is emerging as the workings of most of the types of ion channels underlying cardiac action potentials are elucidated. 35,36 The various long-QT syndromes are the first genetically determined arrhythmias known to be caused at the molecular level by defects in myocardial ion channels (Fig. 5). The congenital long-QT syndrome has an estimated incidence of 1 in 10,000 to 1 in 15,000. It is characterized by prolongation of the QT interval Vol ume 336 Numbe r 22 1581 The New Engla nd Journa l of Medicine A C LQT1 (11q15. 5) KvLQT1 IKs C Long-QT Syndrome Prolongation of QT (QTc 460 msec1/2) Syncope Sudden death N 1 581 Cell membrane LQT2 (7q35–36) HERG IKr Prolonged QT N 1 C 1159 LQT3 (3q21–24) Torsade de pointes II III IV SCN5A INa C P N 1 2016 KPQ P P P P B 47 mV 1 0 Current clamp 85 mV 0 100 2 Prolonged cardiac action potential 3 LQT4 (4q25–27) 4 ? 200 300 400 M illiseconds 500 corrected for heart rate (QTc) to more than 460 msec1/2, and it is an important but relatively rare cause of sudden death in children and young adults (Fig. 5A). The majority (two thirds) of persons with the long-QT syndrome are identified during routine electrocardiographic screening or after the evaluation of a primary relative who is affected. Approximately one third of subjects are identified during a clinical evaluation for unexplained syncope or cardiac or respiratory arrest. These subjects are at an annual risk of 5 percent for an abrupt syncopal episode. Without treatment, symptomatic subjects have 1582 May 2 9 , 1 9 9 7 a 10-year mortality rate approaching 50 percent. Often the arrhythmia is a torsade de pointes polymorphic ventricular tachycardia, typically triggered by adrenergic arousal. 37 Genetic origins were suggested for this syndrome by descriptions both of the autosomal recessive form associated with congenital deafness (Jervell and Lange-Nielsen syndrome)38 and of an isolated autosomal dominant form (Romano– Ward syndrome). 9,40 Substantial progress has been made toward elucidating the molecular basis of the most common inherited subtypes of the long-QT syndrome (Fig. M EC H A NIS MS OF D IS EASE Figure 5. The Long-QT Syndrome. A person with the long-QT syndrome may have unexplained syncope, seizures , or sudden death (Panel A). More likely, the person will be asymptomatic and identified by electrocardiographic screening during a routine evaluation or the screening of a primary relative who is symptomatic. The strict electrocardiographic definition of a prolonged QT interval varies according to age and sex, but generally a QT interval corrected for heart rate (QTc) greater than 460 msec1 ? 2 is considered abnormal. According to Bazett’s formula, the QTc is calculated by dividing the QT interval by the square root of the R-R interval. In patients with the long-QT syndrome, the T-wave morphology is often abnormal. This base-line rhythm can degenerate into a polymorphic ventricular tachycardia, classically a torsade de pointes, as shown here, after a stimulus that is not precisely understood but that often takes the form of adrenergic arousal. The prolonged QT interval as measured on the electrocardiogram results from an increased duration of the cardiac action potential (Panel B). The ventricular action potential is maintained at a resting membrane potential (approximately 85 mV) by inwardly rectifying potassium currents (IK1, phase 4). Once an excitatory stimulus depolarizes the cell beyond a threshold voltage (for example, 60 mV), sodium currents are activated that quickly depolarize the cell (INa, phase 0). These sodium channels are rapidly inactivated, allowing transient potassium currents to return the action potential to the plateau voltage (phase 1). The plateau lasts about 300 msec and provides time for the heart to contract. The plateau is maintained by the competition between outward-moving potassium currents and inward-moving calcium currents (phase 2). Progressive inactivation of calcium currents and increasing activation of potassium currents repolarize the cell to the resting membrane potential (phase 3). On a molecular basis, the autosomal dominant LQT1 and LQT2 are caused by defects in potassium-channel genes (KvLQT1 and HERG) involved in phase 3 repolarization (Panel C). LQT3 is caused by a defective sodium-channel gene, SCN5A. A common SCN5A mutation in families with LQT3 involves a deletion of three amino acids ( KPQ) in the III–IV cytoplasmic linker loop, which is known to regulate inactivation. The mutant sodium channel fails to become completely inactivated, resulting in sustained depolarization and prolonging the cardiac action potential. The linear topology of the proteins responsible for LQT1, LQT2, and LQT3 is shown, with the amino acids numbered beginning with the N-terminal - a total of 581, 1159, and 2016 amino acids, respectively. The chromosomal locations for these genes are shown in parentheses. 5C). 2,36 Recent studies of 16 families with chromosome-II–linked long-QT syndrome type 1 (LQT1) implicated KvLQT1, a 581-amino-acid protein with sequence homology to voltage-activated potassium channels. 41 One intragenic deletion and 10 missense mutations were identified. The combination of the KvLQT1 and ISK subunits (the latter of which contains 130 amino acids, also known as minK) appears to reconstitute the cardiac IKs current. 42,43 IKs (â€Å"s† denotes â€Å"slow†) is one of the principal delayed-rectifying potassium currents responsible for phase 3 repolarization in the heart (Fig. 5B). LQT1 may account for half the incidence of the long-QT syndrome in its autosomal dominant forms. Mutations in a second potassium channel, the human ether-a-go-go–related gene (HERG), have been identified in subjects with the long-QT syndrome type 2 (LQT2), which has been linked44,45 to chromosome 7q35–36. HERG is responsible for the other major potassium current (IKr [â€Å"r† denotes â€Å"rapid†]) that participates in phase 3 repolarization. It is a unique voltage-gated potassium channel; its secondary structure is that of a typical voltage-activated (Kv) potassium channel (Fig. 3A), but it behaves more like an inwardly rectifying (Kir) potassium channel. 6 The role of HERG in normal cardiac physiology appears to be to suppress depolarizations that lead to premature firing. Subjects with LQT2 may therefore be prone to sudden cardiac death, because they lack protection from arrhythmogenic afterbeats. Class III antiarrhythmic drugs block HERG channels. In addition, antihistamines such as terfenadine and antifungal drugs such as ketoconazole have been implicated in acquired cases of the long-QT syn- drome because of their ability to block IKr (HERGmediated) current. The third subtype of the long-QT syndrome (LQT3) has been linked to the gene for the cardiac sodium channel (SCN5A) on chromosome 3p21– 24. 47 This channel is responsible for the fast upstroke of the cardiac action potential (phase 0, Fig. B), which ensures contractile synchrony by causing the potential to spread rapidly throughout the heart muscle. A deletion of three amino acids, KPQ1505– 1507, in a region thought to control rapid inactivation has been demonstrated in LQT3-linked families. The mutant sodium channel fails to inactivate completely, resulting in reopenings of the channel and long-lasting bursts of channel activity. 48,49 The resulting prolonged inward current lengthens the action potential (and thus the QT interval). Finally, a fourth heritabl e type of long-QT syndrome (LQT4) has been linked to chromosome 4q25–27. Its causative gene has not been identified, although a gene encoding a calcium–calmodulin kinase has been proposed. 0 Current therapies for the long-QT syndrome include b-adrenergic–antagonist drugs, cardiac pacing, and left cervicothoracic sympathectomy. The majority of families with heritable long-QT syndrome have type 1, 2, or 3, offering the prospect of genetic screening and directed antiarrhythmic therapy. Theoretically, therapies that augment potassium-channel activity may be used in subjects with potassiumchannel defects (LQT1 and LQT2),51 and those with sodium channel–linked defects (LQT3) may benefit from drugs that decrease sodium-channel activation (such as mexiletine). 52 Vol ume 336 Numbe r 22 1583 The New Engla nd Journa l of Medicine TABLE 2. ION CHANNELS AND DRUGS THAT AFFECT THEM. Calcium channels Antianginal drugs (amlodipine, diltiazem, felodipine, nifedipine, verapamil) Antihypertensive drugs (amlodipine, diltiazem, felodipine, isradipine, nifedipine, verapamil) Class IV antiarrhythmic drugs (diltiazem, verapamil) Sodium channels Anticonvulsant drugs (carbamazepine, phenytoin, valproic acid) Class I antiarrhythmic drugs IA (disopyramide, procainamide, quinidine) IB (lidocaine, mexiletine, phenytoin, tocainide) IC (encainide, flecainide, propafenone) Diuretic drugs (amiloride) Local anesthetic drugs (bupivacaine, cocaine, lidocaine, mepivacaine, tetracaine) Chloride channels Anticonvulsant drugs (clonazepam, phenobarbital) Hypnotic or anxiolytic drugs (clonazepam, diazepam, lorazepam) Muscle-relaxant drugs (diazepam) Potassium channels Antidiabetic drugs (glipizide, glyburide, tolazamide) Antihypertensive drugs (diazoxide, minoxidil) Class III antiarrhythmic drugs (amiodarone, clofilium, dofetilide, N-acetylprocainamide, sotalol) Drugs that open potassium ch annels (adenosine, aprikalim, levcromakalim, nicorandil, pinacidil) TARGETING ION CHANNELS Drugs that target ion channels include calciumchannel blockers (used in patients with hypertension), potassium-channel blockers (used in patients with non-insulin-dependent diabetes mellitus), some diuretics and antiseizure medications, and essentially all antiarrhythmic drugs (Table 2). Recent progress in the basic understanding of the ATP-sensitive potassium channel (IK. ATP) and the G-protein–activated potassium channel (IK. ACh) shows the opportunities for drug design. The ATP-Sensitive Potassium Channel The IK. ATP current has been characterized in heart, skeletal muscle, pituitary, brain, smooth muscle, and pancreas. 55 In the pancreas, it plays a major part in regulating glucose homeostasis and the secretion of insulin. 56 Rising plasma glucose concentrations increase intracellular concentrations of ATP in islet beta cells, which in turn inhibit IK. ATP channels. As these potassium channels close, the cell’s membrane potential depolarizes away from EK and enters the range in which voltage-dependent calcium channels are activated. The resulting influx of calcium triggers insulin secretion. As plasma glucose concentrations decline, intracellular concentrations of ATP decrease and IK. ATP channels become more active, hyperpolarizing the cell, closing the calcium channels, and terminating the secretion of insulin. Oral hypoglycemic drugs (such as glyburide) bind to the sulfonylurea receptor to inhibit the activity of IK. ATP and promote the secretion of insulin. 57 Drugs that open potassium channels include nicorandil, pinacidil, aprikalim, levcromakalim, and diazoxide. In vascular smooth muscle these drugs open IK. ATP channels, hyperpolarize cell membranes, and reduce calcium-channel activity, thus decreasing vascular tone. The drugs are therefore potentially cardioprotective and may provide novel therapeutic approaches in patients with cardiac disease or hypertension. 58-60 The subtype specificity of sulfonylurea receptors (SUR1 in the pancreas and SUR2 in the heart) may be exploited to develop more specific drugs. The G-Protein–Activated Potassium Channel The ATP-sensitive potassium channel IK. ATP is a multimeric complex of inwardly rectifying potassiumchannel subunits (Kir 6. 2 K. ATP-a) and the sulfonylurea receptor (SUR1 K. ATP-b). 53,54 The genes for both are located on chromosome 11p15. 1. SUR1 binds sulfonylurea drugs. Mutations in the SUR1 gene are responsible for persistent hyperinsulinemic hypoglycemia of infancy. 5,6 Kir 6. 2 is an inwardly rectifying potassium channel. Like other such channels, it has two transmembrane-spanning segments surrounding a pore domain. Expression of both SUR1 and Kir 6. 2 results in a potassium channel that is sensitive to intracellular ATP inhibited by sulfonylurea , drugs, and activated by diazoxide, as is consistent with the known properties of IK. ATP channels in pancreatic beta cells. The cardiac sulfonylurea receptor, SUR2, has a lower affinity for sulfonylurea drugs than does SUR1, and it may form the cardiac IK. ATP channel by combining with a homologue in the Kir 6 family. 1584 May 2 9 , 1 9 9 7 Vagally secreted acetylcholine binds to cardiac muscarinic type 2 receptors. Activating these G-protein– linked receptors slows the heart rate by opening a potassium-selective ion channel (IK. ACh) composed of G-protein–activated inwardly rectifying Kir subunits. In turn, IK. ACh decreases spontaneous depolarization (pacemaker activity) in the sinus node and slows the velocity of conduction in the atrioventricular node. 61,62 Muscarinic stimulation of IK. ACh can terminate arrhythmias, particularly supraventricular tachycardias, providing the basis for carotid massage and other vagotonic maneuvers. 5 Another G-protein–linked receptor agonist, adenosine, activates the same cascade in atria and pacemaking cells through type 1 purinergic receptors. Because muscarinic stimulation has many systemic effects, adenosine has become a favored treatment for supraventricular tachycardia; it is also useful in determining the underlying arrhythmic mechanism (usually a reentrant one). 63 The molecular mechanism of the activation of IK. ACh (IK. G) is known. 64 Cardiac IK. ACh is a heteromultimer of two inwardly rectifying potassium-channel subunits, GIRK1 (Kir 3. 1) and GIRK4 (CIR or Kir 3. 4),65 and it is activated after the direct binding of the bg subunits of G protein (Gbg). 66 Similar IK. ACh currents and GIRK proteins are present in the brain. M EC H A NIS MS OF D IS EASE Neuronal GIRK channel proteins are formed by heteromultimers of GIRK1 and GIRK2 in the cerebellum, midbrain, and cortex. In homozygous weaver mice that have profound ataxia due to the loss of granule-cell neurons during cerebellar development, a single point mutation in the highly conserved pore region of GIRK2 results in granule-cell death and failure of migration. The mutated weaver-mouse channel loses its potassium-ion selectivity and sensitivity to Gbg, converting a regulated repolarizing potassium channel into a constitutively active, nonselective depolarizing channel and resulting in increased excitotoxic cell death. 67 CONCLUSIONS A growing number of heritable diseases are known to be caused by ion-channel mutations. Chloridechannel defects underlie cystic fibrosis, certain myotonias, and heritable nephrolithiasis. Mutant sodium channels give rise to the long-QT syndrome and other myotonias, potassium-channel malfunction increases susceptibility to arrhythmias, and calciumchannel mutations can result in hypokalemic periodic paralysis, malignant hyperthermia, and central core storage disease. Identifying the structural framework of the major ion-channel proteins and resolving the precise relations between structure and function should make it possible to develop new therapies for patients with these disorders. We are indebted to David A. 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Gribkoff VK, Champigny G, Barbry P Dworetzky SI, Meanwell NA, Lazdunski M. The substituted benzimidazolone NS004 is an opener of the cystic fibrosis chloride channel. J Biol Chem 1994;269:10983-6. 30. Howard M, Frizzel RA, Bedwell DM. Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat Med 1996;2:467-9. 31. Sato S, Ward CL, Krouse ME, Wine JJ, Kopito RR. Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J Biol Chem 1996;271:635-8. 32. Voilley N, Lingueglia E, Champigny G, et al. The lung amiloride-sensitive Na channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning. Proc Natl Acad Sci U S A 1994;91:247-51. 33. Knowles MR, Olivier KN, Hohneker KW, Robinson J, Bennett WD, Boucher RC. Pharmacologic treatment of abnormal ion transport in the airway epithelium in cystic fibrosis. Chest 1995;107:Suppl:71S-76S. 34. Knowles MR, Clarke LL, Boucher RC. Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. N Engl J Med 1991;325:533-8. 35. Ackerman MJ, Clapham DE. Normal cardiac electrophysiology: understanding the action potential in the human heart. In: Chien K, ed. Molecular basis of heart disease: a companion to Braunwald’s heart disease (in press). 36. Roden DM, Lazzara R, Rosen M, Schwartz PJ, Towbin J, Vincent GM. Multiple mechanisms in the long-QT syndrome: current knowledge, gaps, and future directions. Circulation 1996;94:1996-2012. 37. Moss AJ, Robinson JL. Long QT syndrome. Heart Dis Stroke 1992; 1:309-14. 38. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death. Am Heart J 1957;54:59-68. 39. Romano C, Gemme G, Pongiglione R. Aritmie cardiache rare dell’eta’ pediatrica. Clin Pediatr 1963;45:656-83. 40. Ward OC. A new familial cardiac syndrome in children. J Ir Med Assoc 1964;54:103-6. 41. Wang Q, Curran ME, Splawski I, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 1996;12:17-23. 42. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G. K VLQT1 and IsK (minK) proteins associate to form the IKs cardiac potassium current. Nature 1996;384:78-80. 43. Sanguinetti MC, Curran ME, Zou A, et al. Coassembly of K VLQT1 and minK (IsK) proteins to form cardiac IKs potassium channel. Nature 1996;384:80-3. Vol ume 336 Numbe r 22 1585 The New Engla nd Journa l of Medicine 44. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 1995;80:795-803. 45. Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 1995;81:299-307. 46. Smith PL, Baukrowitz T, Yellen G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature 1996;379:833-6. 47. Wang Q, Shen J, Splawski I, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995;80: 805-11. 48. Bennett PB, Yazawa K, Makita N, George AL Jr. Molecular mechanism for an inherited cardiac arrhythmia. Nature 1995;376:683-5. 49. Dumaine R, Wang Q, Keating MT, et al. Multiple mechanisms of Na channel-linked long-QT syndrome. Circ Res 1996;78:916-24. 50. Schott J-J, Charpentier F, Peltier S, et al. Mapping of a gene for long QT syndrome to chromosome 4q25-27. Am J Hum Genet 1995;57:111422. 51. Compton SJ, Lux RL, Ramsey MR, et al. Genetically defined therapy of inherited long-QT syndrome: correction of abnormal repolarization by potassium. Circulation 1996;94:1018-22. 52. Schwartz PJ, Priori SG, Locati EH, et al. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na channel blockade and to increases in heart rate: implications for gene-specific therapy. Circulation 1995;92:3381-6. 53. Inagaki N, Gonoi T, Clement JP IV, et al. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 1995;270: 1166-70. 54. Aguilar-Bryan L, Nichols CG, Wechsler SW, et al. Cloning of the b cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science 1995;268:423-6. 55. Terzic A, Jahangir A, Kurachi Y. Cardiac ATP-sensitive K channels: regulation by intracellular nucleotides and K channel-opening drugs. Am J Physiol 1995;269:C525-C545. 56. Ashcroft FM. Adenosine 5 -triphosphate-sensitive potassium channels. Annu Rev Neurosci 1988;11:97-118. 57. Ashcroft SJ, Ashcroft FM. The sulfonylurea receptor. Biochim Biophys Acta 1992;1175:45-59. 58. Lopez JR, Jahangir R, Jahangir A, Shen WK, Terzic A. 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Multiple Choice Tests Strategies for Students

Multiple Choice Tests Strategies for Students Multiple choice tests are one of the most popular forms of assessment utilized by classroom teachers. They are easy for teachers to construct and score. Mastering multiple choice exams are one part mastery of content and one part skillful test taking. The following multiple choice tests strategies will help students improve their scores on a multiple choice assessment. These strategies are designed to increase the chances of a students answer being correct. Making it a habit of using each of these strategies on a multiple choice test will make you a better test taker. Read the question at least two times before you look at the answer. Then read the answer choices at least two times. Finally, re-read the question one more time.Always cover up the possible responses with a piece of paper or with your hand while you read the stem or body of the question. Then, come up with the answer in your head before looking at the possible answers, this way the choices given on the test wont throw you off or trick you.Eliminate answers you know arent right. Every answer you can eliminate increases your odds of getting the question correct.Slow down! Read all the choices before choosing your answer. Do not assume that the first answer is correct. Finish reading all the other choices, because while the first may fit, a latter one may be the better, more correct answer.If there is no guessing penalty, always take an educated guess and select an answer. Never leave an answer blank.Do not keep on changing your answer; usually your first choice is the correct one unles s you misread the question. In All of the above and None of the above choices, if you are certain one of the statements is true do not choose None of the above or one of the statements are false do not choose All of the above.In a question with an All of the above choice, if you see that at least two correct statements, then All of the above will be the correct answer choice.Tone can matter. A positive answer choice is more likely to be correct over a negative answer choice.Wordiness is a good indicator. Usually, the correct answer is the choice with the most information.If all else fails, choose response (b) or (c). Many instructors subconsciously feel that the correct answer is hidden better if it is surrounded by distractors. Response (a) is usually least likely to be the correct one.Stay within the lines. Be sure that you have filled the appropriate bubbles carefully WITH A #2 PENCIL. Be sure that there are no stray marks.Take the time to check your work before you hand in the answer sheet. On a timed test, utilize every second of time that you have to go over your answer choices as much as possible. On an untimed test, check over everything multiple times.

Response paper 7, chinese literature Essay Example | Topics and Well Written Essays - 250 words

Response paper 7, chinese literature - Essay Example The first two stanzas describe the stars, weather, skies, and wind with an accepting attitude. The writer knows that weather and the stars cannot be changed, so the narrator accepts the storm or calm weather as a fact of life, looking at the beauty of nature without any complaint. The unknown causes of the universe cannot be understood by the narrator, so acceptance and appreciation is the resulting attitude. After the passive description of the surroundings, the narrator states an old man’s wish to sail away. This stanza is influenced by the Zihuangzi’s thought of a man’s impassive look at life. The old man wishes to sail, but both the narrator and old man understand that is not the old man’s Dao. In return, the narrator’s suffering in the jungle is accepted as the narrator’s Dao. The trip was balanced by the acceptance of good and bad. Throughout this whole poem Zihuangzi’s thought is a main influencing

Air pollution in China Essay Example | Topics and Well Written Essays - 1000 words

Air pollution in China - Essay Example country claiming that the country would continue to grow its economy relying on the energy inefficient industries and using the polluting agents (Feng, 1999). However, the studies claim that the cost of pollution would oppose the development a feature that has begun stagnating development endeavors in the country as the discussion below portrays. The introductory paragraph above states that pollution is costly and deters infrastructural development and economic growth in the country. China’s economy has grown within the last few years owing to the rapid industrialization of the country. China is among the largest consumers of fossil fuels in the world with most of the industries in the country running on petroleum products. While industrialization has fostered the economic growth of the country, such endeavors have contributed to different forms of pollution thus culminating in the current state of affairs. Currently, the rate of pollution has reached the highest level deterring visibility owing to fog. Such high levels of pollution have begun affect the country’s economic growth by making the country, a country that was once the leading global investment destination, lose on foreign investors most of who site the health implications of the intense pollution. Industries in China are the leading pollutants. The country has millions of industries that run of fossil fuels thereby emitting large amounts of carbon monoxide and carbon dioxide among other poisonous gases. Cities in the northern parts of the country are more polluted than in any other parts of the country owing to high number of industries in such regions. China for example is the leading exporter of steal globally (Innes & Hassan, 2000). Steel and cement industries are among the companies located in the northern parts of the country. Cement and steel industries in the country contribute to pollution owing to the large-scale evacuation processes they carry out coupled with an equally large-scale

Role of Emotional Intelligence Essay Example for Free

Role of Emotional Intelligence Essay Summary: This article discusses the correlation of a leaders Emotional Intelligence (â€Å"the ability to understand and manage moods and emotions in the self and others†) (George) and how it plays a role in how effective that manager is. The author first relates how emotions, moods and feelings play a part in how humans deal with each other on a day to day basis. Ms. George points out that positive moods and emotions can have a positive effect on how we deal with life, and on the flip side how negative moods and emotions can have the opposite effect in our social and work lives. She states that â€Å"Feelings are intimately connected to the human experience. Feelings are intricately bound up in the ways that people think, behave, and make decisions.† Many people with the inability to show emotion find life difficult as even the smallest decisions are hard to make with no gage of how others may react or â€Å"feel† about your choices. The article is not so much about how leaders behave but more so how effective that behavior is in understanding their own and others emotions and moods. The author states there are four different attributes of one’s emotional intelligence; the appraisal and expression of emotion; the use of emotion to enhance cognitive processes an decision making; knowledge about emotions; and the management of emotions. The article explores each of these attributes and how having these skills can be useful to a leader in dealing with their peers and subordinates. In all the article points to evidence that good leaders also have a higher emotional intelligence (whether they are born with it or whether they learn it). It does not state that EI is the only determining factor when comparing a good leader only that studies show that there is a correlation. Behavioral Issue: The behavioral issue is how one can use their knowledge of moods and emotions to shape the way they and others react to any given situation. Emotional intelligence in leaders can therefore bring forth the desired results of the organization that they work for. The four different attributes of EI can be used to utilize leaders and those that they lead.  Leaders with EI can use the attribute of appraisal and expression of emotion, which â€Å"ensures that people are able to effectively communicate with others to meet their needs and accomplish their goals or objectives.† A leader who uses the knowledge of emotion, will understand what determines what a person’s mood might be (such as knowing that delivering bad news will probably bring on a bad mood) and what the consequences of these moods might be (moods may linger for some time increasing negative attitudes and poor results of the sought after goal). A manager with good EI skills can help enhance â€Å"cognitive processes and decision making† skills of others. If a leader can predict or imagine what the reaction of someone else could be given two different actions will have the ability to make a decision as to which action to go with to bring out the desired result for his company. A leader who can manage his own feelings may well be able to manage or evoke desired emotions from others (getting his team motivated and excited about a new project) and this can be instrumental in meeting deadlines and the projected goals of his team. In short, emotional intelligence can be very useful to a manager who is trying to be an effective leader. Opinion: In my opinion I think the article touches on a very interesting subject. I believe the idea of emotional intelligence is integral to one being an effective manager. This article states many instances when the ability to determine and understand your own feelings, emotions and moods as well as that of others can in effect shape the mood and actions of others. â€Å"Truly effective leaders are also distinguished by a high degree of emotional intelligence, which includes self-awareness, self-regulation, motivation, empathy, and social skill.† (Goleman, 2004) I have personally known managers who display good EI (one who seemed to know how to always motivate me to do the best job possible no matter how lowly the task) and those who are most definitely lacking in the same skills (one who would berate me in front of customers and co-workers). â€Å"Every businessperson knows a story about a highly intelligent, highly skilled executive who was promoted into a leadership position only to fail at the job. And they also know a story about someone with solid—but not extraordinary—intellectual abilities and technical skills who was promoted into a similar position and then soared†. (Goleman, 2004) I am finding that I am firm believer in the  use of EI tests prior to hiring is a solid business decision. That way, when social skills are needed for the open position, you are getting an employee that matches all of your needs not just the technical ones. Relevance to the Study of Organizational Behavior: All businesses or organizations need managers to help shape their employees attitudes and behavior to ensure their desired outcomes. Managers who possess emotional intelligence help to make this possible in the most effective way possible. This is relevant because it deals with employees and with that, employee emotions and how they will react to a manager with good emotional intelligence. Managers who can motivate, or actively manage the workforce by using EI whether natural or learned will ultimately make the company money. Although EI is not required for some types of jobs (jobs that require little to no human contact) there are still many jobs where a manager’s emotional intelligence can be utilized and can make a difference to the bottom line of the company, which is usually the desired outcome. References George, J. M. (n.d.). Emotions and Leadership: The Role of Emotional Intelligence. Goleman, D. (2004). What Makes a Leader? Retrieved from Harvard Business Review: http://hbr.org/2004/01/what-makes-a-leader

Androcentrism Essay -- essays research papers

Androcentrism When I started to think about what to write for this paper I wanted to learn more about androcentrism. Well, I guess I know what it means, but I wanted to see what it means to other people. In Random House Webster’s Unabridged Dictionary 2nd Edition the definition for androcentric is centered on emphasizing, or dominated by males or masculine interests. Then I went online and mostly the same definition. The only definition that I found that said anything about women was at http://dictionary.reference .com. It read: centered or focused on men, often to the neglect or exclusion of women. I started to wonder what religious dictionary’s thought of androcentrism. So I looked up some religious dictionaries. After about 10 of them I gave up because I came empty handed. It’s like they didn’t believe it existed. But, to my surprise I did find a definition to androgyny in a few of them. And let’s not forget my personal definition: Men are better than women. A lthough I do not think this is true, that is just how I see androcentrism.   Ã‚  Ã‚  Ã‚  Ã‚  Now I am going to talk about the levels of androcentrism that make the study of religions difficult. I am going to refer a lot to the book Feminism and Religion by Rita M. Gross. The first level of andrcentrism is the history. â€Å"As in the study of contemporary religions, many conventional historians are most interested in those who wielded power, which means that not only women, but other disempowered groups hav...

Legal and Political Aspects of the Business

Pick an administrative agency of either the Federal or a State government. Find where the current and proposed regulation changes for that agency are located on the internet. (i.e. the Federal Register or the State Administrative Agency website.) Regulations.gov is a good place to begin your research. Pick one proposed regulation change currently under consideration (if you find one which has already closed out, but interests you, you can use that, instead) and write the following regarding it: 1. State the administrative agency which controls the regulation. Explain why this agency and your proposed regulation interests you (briefly). Will this proposed regulation affect you or the business in which you are working? If so, how? Submit a copy of the proposed regulation along with your responses to these five questions. The proposed regulation can be submitted as either a separate Word document (.doc) or Adobe file (.pdf). This means you will submit two attachments to the Week 2 Dropbox: (1) a Word doc with the questions and your answers and (2) a copy of the proposed regulation you used for this assignment. The administrative agency I choose is the Social Security Administration and the proposed regulation is â€Å"Amendments to Regulations Regarding Withdrawal of Applications and Voluntary Suspension of Benefits†.I selected this agency because as most of us deal with it and some way or the other everyone in the family will affected by the proposed rules of it. Coming to this rule ,it is so interesting that how can they limit the period of applying and taking their rights away. 2. Describe the proposal/change. Basically workers have the right to choose when to apply for old age benefits.So depending on the time they apply the number of benefits will be decreased or increased accordingly. According to this proposed regulation they are limiting the time for the withdrawal of old age benefits applications. They only allow only one withdrawal for lifetime and also limit the voluntary suspension benefits.And they say that by doing these changes to the current policies they can avoid the misuse of them. 3.Write the public comment which you would submit to this proposal. If the proposed regulation deadline has already passed, write the comment you would have submitted. Explain briefly what you wish to accomplish with your comment. I am not favor of this proposed rule because my uncle who is about to retire in few years when he is 62 and wanted to postpone to apply for old age benefits at 70.This is because it will increase the benefits.At present he is good and planning to work few more years after retiring so that he can take care of his sister who is suffering from cancer.By this proposed rule he has to apply for the benefits within 12 month period after he retires which makes him out of money when he actually is in need of it.Old age people don’t have any one to take care of them and they all expect more benefits and they know when they do need the benefits.If they think that are they proposing this rule to not make it misuse or abuse they should find out the percentage of people who are suffering from it.

Motivation and Performance Theories in Relation to New Zealand Post

A simple game of bingo, if analysed closely, can be shown to be a tedious task consisting of a repetitive action that occurs after being prompted by a repetitive stimulus. The skill level needed to make that action is low, and the variability in the rules of the game rarely changes. This game is not unlike many of the jobs that can be classified as having low motivational performance. So why do people not only enjoy playing games like bingo, but actually pay money to have the pleasure? The answer directly points to the motivating factors of monetary rewards, which is the stimulus for the individual†s performance. In this essay I will discuss the theory behind â€Å"Motivation† and â€Å"Performance† in relation to New Zealand Post and the theoretical ideals that their management should adopt with employees. There are many theories regarding motivation with the most prevalent being the theories of Abraham Maslow and Frederick Herzberg. It is important to understand these theories and their implications to accurately comment on reinforcement theories of motivation. According to Maslow†s hierarchy of needs, there are five classes: (1) physiological, (2) safety, (3) social, (4) esteem, and (5) self-actualisation. (Karen. P. Harlos Lecture Notes) each lower level need must be satisfied before an individual experiences higher level needs. Also, as Hall, Batley, Elkin, Geare, Johnston, Jones, Selsky and Sibbald (1999) found that Maslow hypothesized that as physiological, safety, social, and esteem needs were satisfied, they ceased to motivate, while the self-actualisation needs actually motivate an individual more as they are satisfied (Hall et al. 999). Herzberg used this theory as a base to build his motivation-hygiene theory, which ties Maslow†s needs to on the job achievement. The hygiene elements relate to low needs (physiological, safety, and social)(Harlos 2000). For an individual, hygiene conditions include company policy and administration, supervision, relationships with peers and supervisors, work conditions, salary, status, and security. These, according to Herzberg account for 69% of the factors that cause employee dissatisfaction or lack of motivation. The motivation conditions, which include achievement, the job itself, recognition, responsibilities, and personal growth, accounted for 81% of the factors that contributed to job satisfaction. The hygiene conditions are extrinsic factors (behaviour that is performed for material or social rewards as defined by Harlos 2000) while the motivation conditions are intrinsic factors (behaviour that is performed for its own sake not for material or social rewards as defined by Harlos 2000), and the only way to sustain motivation toward organizational goals is through the achievement of intrinsic outcomes. Each of these theories has proven to contain ideas consistent with human nature, but each also has its limitations within organizational settings. Because lower order needs are generally satisfied in the workplace today, managers have to deal with how to provide esteem and self-actualisation to their employees, and that can be a vague concept to a manager who demands results immediately. Also, studies demonstrate that different workers are motivated by different factors be them intrinsic or extrinsic. In relation to New Zealand Post the above theories can be applied to achieve an excellent level of motivation within the organization, however there are potential disadvantages also, where the employees may get over-motivated or become too empowered and thus create divisions within the organization. In terms of Maslow†s theory, the five levels of needs could be ensured by mangers of NZ Post and overall by the corporate planners of NZ Post by the following; in terms of physiological needs, money is the driving factor here as it provides the a means of achieve food, shelter, warmth and sleep, thus that management role is very limited, as it is controlled to a degree by relevant laws of the country. However those above the management who set wages must be careful not to set wages too low, otherwise workers will become grossly dissatisfied and look elsewhere to achieve their basic needs (Hall et al. 999). At the safety level NZ Post can provide their employees with agreeable contracts and work benefits such as health care. A work environment that is considered safe as well as adequate ongoing training is another aspect, also assurances of long-term employment (Hall et al. 1999). Social level issues can be resolved by NZ Post by organising teams maybe by regions and encouraging group satisfaction, or perhaps even making sure contact is established by way of team sports days, or annual picnic†s etc, any activity that ensures worker contact (Hall et al. 999). The next level is perhaps the most crucial in terms of how much NZ Post management is concerned, management may be able to fill esteem needs of the employee by showing recognition of a job well done, which may lead to a internal structure whereby levels of achievement are reached, and as the employee reaches these levels they may gain more responsibility within the organisation (Hall et al. 1999). Self actualisation needs in terms of what management can do for employees to reach this stage, entirely depend on the individual, and the previous stage, as itself esteem is realised then self actualisation becomes of more importance, and so the employee is self-motivated and the role of the NZ Management is merely one of maintenance (Hall et al. 1999). The above are all very good in theory, but in practice the implications of some of these theories for an individual and for the organisation can be crucial. NZ Post Management couldn†t be blamed if they felt the offering of money to an employee over and above what the individual needs to satisfy there needs would result in that individual working harder, however what is more likely to happen is the individual isn†t motivated anymore by that factor, and is instead motivated by esteem needs, as cited in Hall et al. 2000) â€Å"A satisfied need is not a motivator† The application of the Herzberg two-factor model is in practice much more involved that I first thought, there seems to be a large amount of criticism about Herzberg, which I will attempt to briefly outline, and thus if NZ Post was to adapt this theory it may not provide the right answer to any problems they may be facing. Firstly there has been research done into the methodology of Herzberg's research, it seems that by asking the questions in the way that they did it was only natural that individuals would attribute the good things about the job to themselves and the bad things to the organisation (as suggested by Vroom 1964 cited in Thomson 1989). So the good things simply became meting challenges, getting promoted and assuming responsibility, whereas bad things were in affect always the fault of the organisation. Thus it was reasonable for individuals to attribute their lack of performance as being a result of poor organisational structure or communication, or poor wages or bad working conditions, therefore Herzberg†s findings were more a result of the way the questions were asked and not altogether an indication of what motivated individuals at work. The second criticism that arises is whether or not it is possible to clearly â€Å"distinguish between motivator and hygiene variables in the way that two factor theory does. † (Thomson 1989 pg 164). At times factors like the gender of the worker and the structure of the organisation tends to influence whether or not a job characteristics acts as a motivator or a hygiene, thus the distinction is not as clear cut as Herzberg†s theory would suggest. Finally the two-factor theory just doesn†t take into consideration the differences between individuals, its just known that individuals do not always react in a similar fashion, for the same work characteristics which will motivate one individual may not necessary motivate another. I suggest for NZ Post to be able to maintain the calibre of people they strive for, and to provide tools to develop and grow, the best way to create the desired environment and create the best management would be to adopt Maslow†s theories, as it allows for more of an individual touch to individual situations. McGregor developed an additional theory on human behaviour, motivation, and especially performance in the late 1950†³s. His theories X and Y and were based on assumptions made regarding the â€Å"system† and individuals. In short, in Theory X (the most common management practice) management organizes all elements of production, motivates and controls employee behaviour to fit the needs of the organization, and without this intervention, employees would be indifferent to changing organizational needs. McGregor further assumes that managers believe that the average employee is by nature are lazy, dislike work, want security and dislike responsibility (as cited by Harlos 2000). McGregor†s alternative to Theory X was Theory Y. This theory made the assumptions that management has the responsibility for organizing the elements of production, people are not by nature passive, but become so as a result of experiences, management should enable employees to develop their motivational characteristics, and that it is essential for management to arrange organizational conditions in a manner where employees can achieve their own goals by directing their personal effort towards organizational objectives. The contrast between X and Y solely relates to who controls human behaviour. Theory X touts external control, and Theory Y promotes a self-fulfilling prophecy and that Theory Y management will breed Theory Y employees and vice-versa. In the application of McGregor†s theories an obvious pitfall is that obviously given the choice management will opt for Theory Y, however the application can result in a very different outcome. Theory Y places an unrealistic amount of burden on the management, and thus they have to sometimes resort to Theory X as no matter how much nurturing or inspiration managers give to employees, there will always be some who just have no desire to work, and show little or no initiative. So NZ Post may run many seminars to attempt to increase performance, or empower those who management feel need a performance boost, yet inevitably those who have no desire to perform better will just not respond to any of these performance motivators and hence management will have to resort to Theory X management to get these employees to work as they should be. Another problem may be with those employees who have been part of the organisation for a number of years, and a new fresh inspirational manager comes along who has been to all the courses and seminars and has used all the theories, and yet these employees are so used to old school Theory X management, they will just simply not be able to conform to this new Theory Y management style, as suggested in Hall et al. (1999) In conclusion I have outlines both Maslow†s and Herzberg†s theories in relation to motivation and McGregor†s theories in relation to performance. I also have suggested ways in which NZ Post could apply these theories to enable them to better fulfil their corporate profile statement. I suggested that perhaps Herzberg†s theory would not be best suited to NZ Post due to the many flaws in the application of his theory and that Maslow†s theory in practice would enable a better fufilment of the corperate profile statement.