(65)--医学细胞生物学Chapter14IonsandVoltages.pdf

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1、P1:GIGWY001-14WY001-Bolsover-v2.clsSeptember 15,200320:614IONS AND VOLTAGESWedescribedinChapter2howmembranesarecomposedofphospholipidsarrangedsothattheir hydrophobic tails are directed toward the center of the membrane,while the polar hy-drophilicheadgroupsfaceout.Membranesareabarriertothemovementof

2、manysolutes.Inparticular,smallhydrophilicsolutessuchasionsandsugarscannotpassthroughmembraneseasily because,to do so,they would have to lose the cloud of water molecules that formstheir hydration shell(page 21).Two consequences follow from the fact that membranes arebarriers.First,thecompositionofth

3、eliquidononesideofamembranecanbedifferentfromthe composition of the liquid on the other side.Indeed,by allowing cells to retain proteins,sugars,ATP,and many other solutes,the barrier property of the cell membrane makes lifepossible.Table 14.1 shows how five important ions have different concentratio

4、ns in cytosoland extracellular medium.Second,the cell must make proteins called channels and carrierswhose job it is to help hydrophilic solutes across the membrane.This chapter describes theproperties of membranes,with particular emphasis on their role in energy storage.THE POTASSIUM GRADIENT AND T

5、HE RESTING VOLTAGEIons are electrically charged.This fact has two consequences for membranes.First,themovementofionsacrossamembranewilltendtochangethevoltageacrossthatmembrane.If positive ions leave the cytosol,they will leave the cytosol with a negative voltage,andvice versa.Second,a voltage across

6、 a membrane will exert a force on all the ions present.If the cytosol has a negative voltage,then positive ions such as sodium and potassium willCell Biology:A Short Course,Second Edition,by Stephen R.Bolsover,Jeremy S.Hyams,Elizabeth A.Shephard,Hugh A.White,Claudia G.WiedemannISBN 0-471-26393-1 Cop

7、yrightC?2004 by John Wiley&Sons,Inc.309P1:GIGWY001-14WY001-Bolsover-v2.clsSeptember 15,200320:6310IONS AND VOLTAGESTable 14.1.Typical Concentrations for Five Important Ions in Mammalian Cytosol andExtracellular MediumaIonCytosolExtracellular MediumSodium Na+10 mmol liter1150 mmol liter1Potassium K+1

8、40 mmol liter15 mmol liter1Calcium Ca2+100 nmol liter11 mmol liter1Chloride Cl5 mmol liter1100 mmol liter1Hydrogen ion H+(really H3O+)63 nmol liter1or pH 7.240 nmol liter1or pH 7.4aNote the units n for nano is one million times smaller than m for milli.be attracted in from the extracellular medium.I

9、n this chapter,we will begin to address thequestionofhowionsandvoltagesinteractbyconsideringtheeffectofpotassiummovementson the voltage across the plasma membrane.Potassium Channels Make the Plasma Membrane Permeableto Potassium IonsThe potassium channel(Fig.14.1)is a protein found in the plasma mem

10、brane of almost allcells.It is a tube that links the cytosol with the extracellular fluid.Potassium ions,whichcannot pass through the lipid bilayer of the plasma membrane,pass through the potassiumcytosolextracellularmediumextracellular mediumK+cytosolK+Figure 14.1.The positively charged potassium i

11、on cannot cross the lipid bilayer but passes easilythrough a water-filled tube in the potassium channel.P1:GIGWY001-14WY001-Bolsover-v2.clsSeptember 15,200320:6THE POTASSIUM GRADIENT AND THE RESTING VOLTAGE311channeleasily.Otherionscannotgothrough.Thepreciseshapeofthetube,andthepositionof charged am

12、ino acid side chains within the tube,blocks their movement.The channel isselective for potassium.We saw earlier that the Na+/K+ATPase(page 270)uses the energy of ATP hydrolysisto drive sodium ions out of the cell and,at the same time,brings potassium ions into thecell.This ensures that potassium is

13、much more concentrated in the cytosol than outsidetypically140mmolliter1inthecytosolbutonly5mmolliter1intheextracellularmedium.There is an apparent paradox here.If potassium can pass through the potassium channel,why is this ion much more concentrated inside the cell than outside?Why doesnt all thep

14、otassium rush out?To explain why,we must think about the effects of ion movement ontransmembrane voltage.First a word on nomenclature.All cells have a voltage across theirmembrane when they are not being stimulated.This resting voltage is about 80 mV ina relaxed skeletal muscle cell.As soon as the m

15、uscle is stimulated to contract,there is asudden sharp change in the transmembrane voltage called the action potential(a processdescribed in more detail in Chapter 15).Many cells never change their transmembraneresting voltage.Concentration Gradients and Electrical Voltage Can BalanceA few potassium

16、 ions do escape from the cell through the potassium channel.As they doso,they carry out their positive charge and leave the cytosol with a negative voltage thatattracts positively charged ions like potassium.There is still a tendency for potassium ionstoleavethecelldowntheconcentrationgradient,butth

17、ereisnowanelectricalforcepullingthe positively charged potassium ions back inside.We have met a similar situation before,where we described how a concentration gradient and an electrical force combine to forman electrochemical gradient down which H+ions will rush into bacteria or mitochondria(page 2

18、61).However,in the case of potassium ions at the plasma membrane,the concentra-tion gradient and the electrical force act in opposite directions.As potassium ions continueto leave the cell,carrying out their positive charge and leaving the cytosol at a more andmore negative voltage,the electrical fo

19、rce pulling them back in gets increasingly strong.Soon,the opposing electrical and concentration gradients are equal,and the overall elec-trochemical gradient for potassium is zero.Potassium ions then stop leaving the cell,eventhough they are much more concentrated inside than outside.For every ion

20、present on both sides of a membrane,it is possible to calculate thetransmembrane voltage that will exactly balance the concentration gradient.This voltage iscalled the equilibrium voltage for that ion at that membrane.For potassium at the plasmamembrane of a normal animal cell,the equilibrium voltag

21、e is about 90 mV.The departure of potassium ions through the potassium channels,leaving negativecharge behind,produces the resting voltage across the plasma membrane.Because thepotassium channels are the major pathway by which ions can cross the plasma membraneof an unstimulated cell,the resting vol

22、tage has a value close to the potassium equilibriumvoltage.Insomecells,suchaswhitebloodcells,potassiumchannelsaretheonlychannelsintheplasmamembrane,andpotassiumionsmoveoutuntilthetransmembranevoltagetendingto pull them back in exactly balances their tendency to move out down their concentrationgradi

23、ent.Therestingvoltageofwhitebloodcellsthereforehasavalueequaltothepotassiumequilibrium voltage,about 90 mV.In other cells the situation is more complicated.Inmuscle cells,for instance,the resting voltage is 80 mV;in nerve cells it is 70 mV.Evenin these cells,though,the major influence on the resting

24、 voltage is potassium movementP1:GIGWY001-14WY001-Bolsover-v2.clsSeptember 15,200320:6312IONS AND VOLTAGESthrough its channels,so the resting voltage does not deviate very far from the potassiumequilibrium voltage.The resting voltage set up by potassium movement turns the action of the Na+/K+ATPase

25、into an energetically asymmetrical one.Consider one conversion cycle:onemolecule of ATP is hydrolyzed,three sodium ions are pushed out of the cell,and twopotassium ions move in.Very little of the energy of ATP hydrolysis is used up in movingthe two potassium ions into the cell because the electroche

26、mical gradient for this ion isclose to zero.Although potassium is being moved up a concentration gradient,it is alsobeingpulledinbythenegativevoltageofthecytosol,andthetwoforcescancel.Incontrast,pushingthethreesodiumionsoutofthecellrequiresmoreenergythanwouldberequiredifthecytosolwereatthesamevoltag

27、eastheextracellularfluid.Thesodiumionsarepositivelycharged,so they are attracted by the negative voltage inside the cell,which combines withthe concentration gradient to form a large inward electrochemical gradient.All the energyreleased by ATP hydrolysis is needed to push the three sodium ions up t

28、his large electro-chemical gradient.The presence of the potassium channels,and the resting voltage thatthey set up,means that almost all the energy of ATP hydrolysis by the Na+/K+ATPase isstored in the sodium gradient,while potassium ions are close to equilibrium.fIN DEPTH 14.1 The Nernst EquationAn

29、 ion that can pass across a membrane is acted on by two forces.The first derivesfrom the concentration gradient.The ion tends to diffuse from a region where itis at high concentration to one where it is at low concentration.The second forcederives from the transmembrane voltage.In the case of positi

30、vely charged ionssuch as Na+and K+,the ions tend to move toward a negative voltage.Negativelycharged ions such as Cltend to move toward a positive voltage.For each ionthere is a value of the transmembrane voltage for which these forces balance,and the ion will not move.The ion is said to be at equil

31、ibrium,and this value ofthe transmembrane voltage is called the equilibrium voltage for that ion at thatmembrane.Ion I at concentration IoutsideIon I at concentration Iinsidecytosol at voltageVWhen the forces balance,then ions that move in will neither gain nor loseenergy.This way of describing equi

32、librium is useful because it allows us to setequivalent the effects of the two very different gradients,concentration and volt-age.For concentration,the free energy possessed by a mole of ions I by virtue ofits concentration isG=G0+RT logeIjouleswhere G0is the standard free energy,R is the gas const

33、ant(8.3 J mol1degree1),and T is the absolute temperature.P1:GIGWY001-14WY001-Bolsover-v2.clsSeptember 15,200320:6THE NERNST EQUATION313A mole of I passing in therefore moves from a region where it had a freeenergy ofGoutside=G0+RT logeIoutsidejoulesto one where its free energy isGinside=G0+RT logeIi

34、nsidejoulesOne mole of ions I moving inward therefore gains by virtue of the concentrationgradient free energy equal toRT logeIinside RT logeIoutsidejoulesNow consider the electrical force.The definition of a volt means that one coulombof charge moving across a membrane with a transmembrane voltage

35、of V voltsgains V joules of free energy.However,we are working in moles,not coulombs.One mole of ions has a charge of zF coulombs,where z is the charge on the ionin elementary units.For Na+and K+z is 1;for Ca2+z is 2;and for Clz is 1.Theterm F is a number that relates the coulomb to the mole.It has

36、the value 96,500.One mole of ions I moving inward gains by virtue of the transmembrane voltagefree energy equal tozF VjoulesThis does not mean that an ion always gains energy from the transmembranevoltage when it moves inward:the term zF V can just as easily be negative as posi-tive.When the effects

37、 of concentration and voltage just balance,a mole of ionsmoving inward neither gains nor loses free energy.Hence,at equilibriumRT logeIinside RT logeIoutside+zF Veq=0This can be simplified toVeq=RTzFloge?IoutsideIinside?voltsThis is the Nernst equation.At a typical mammalian body temperature of 37C,

38、theNernst equation can be written in the more convenient form:Veq=62zlog10?IoutsideIinside?mvoltsNote the change in the type of logarithm and the units.“In”and“out”can refer to any two solutions separated by a membrane.Atthe plasma membrane in is the cytosol and out is the extracellular medium,butwh

39、en considering equilibria across the inner mitochondrial membrane in is themitochondrial matrix and out is the intermembrane space.P1:GIGWY001-14WY001-Bolsover-v2.clsSeptember 15,200320:6314IONS AND VOLTAGESTHE CHLORIDE GRADIENTChloride ions(Fig.14.2)are at a lower concentration in the cytosol than

40、in the extracellularmedium.Typically,their concentration in the cytosol is 5 mmol liter1compared with 100mmol liter1in the extracellular fluid.This is because of the resting voltage set up by thepotassium channels.Chloride ions are repelled by the negative voltage of the cytosol.Theyleaveuntiltheirt

41、endencytoenterthecelldowntheirconcentrationgradientexactlymatchestheir tendency to be repelled by the negative voltage of the cytosol.Cl=5 mmol liter180 mVcytosolCl=100 mmol liter1.the negatively charged cytosol pushes the negative chloride ions outwardchloride would move down its concentration but.

42、0 mVFigure 14.2.Chloride is close to equilibrium across most plasma membranes.GENERAL PROPERTIES OF CHANNELSChannelsareintegralmembraneproteinsthatformwater-filledtubesthroughthemembrane.Wehavealreadyintroducedthree:thegapjunctionchannel(page55),porin(page262),andthepotassiumchannel.Channelsthat,lik

43、ethepotassiumchannel,areselectiveforparticularions can set up transmembrane voltages.The gap junction channel(page 55)is much lessselectivethanthepotassiumchannel.Itformsatube,1.5nmindiameter,throughwhichanysolute of Mr 1000 can pass.The gap junction channel is not always open.It opens onlywhenitcon

44、nectswithasecondgapjunctionchannelonanothercell,formingatubethroughwhich solutes can pass from the cytosol of one cell to the cytosol of the other.Channelsthat are sometimes open and sometimes shut are said to be gated.When a gap junctionchannelcontactsanotheronanothercell,itsgateopensandsolutecanpa

45、ssthrough;atothertimes the gate is shut.The usefulness of gating is obvious:if the gap junction channels notcontacting others were open,many solutes,including ATP and sodium,would leak out intothe extracellular fluid exhausting the cells energy currencies.Porin in the outer mitochondrial membrane pl

46、ays an important role in energy conver-sion.It forms a very large diameter tube that allows all solutes of Mr 10,000 to pass andseems to spend a large fraction of time open under most circumstances.This is why theouter mitochondrial membrane is permeable to most solutes and ions.Appendix 1,at theend

47、 of this book,lists all the different types of channels described in this book.It representsonly a small fraction of the total number known.P1:GIGWY001-14WY001-Bolsover-v2.clsSeptember 15,200320:6GENERAL PROPERTIES OF CHANNELS315?Example 14.1Cytochrome cVital But DeadlyWe have described how the elec

48、tron carrier cytochrome c resides in the intermembrane space be-tweentheouterandinnermitochondrialmembranesandhelpstheelectrontransportchaintoconvertenergy as NADH to energy as the hydrogen ion electrochemical gradient across the mitochondrialinner membrane(page 266).Although cytochrome c is a solub

49、le protein of relative molecular mass12,270,it cannot escape from the intermembrane space into the cytosol because porin,the channelof the outer mitochondrial membrane,only allows solutes of Mr 10,000 to pass.Althoughcytochrome c is essential for mitochondrial function,it has another,deadly role.If

50、cytochrome ccomesintocontactwithaclassofcytosolicenzymescalledcaspases,itactivatesthem,turningontheprocessofcellsuicidecalledapoptosis(page417).Undercertainconditions,porincanassociatewithother proteins to form a channel of larger diameter;when this happens,cytochrome c can leak outand the cell dies