The Membrane Potential

Graphicsareusedwithpermissionof: PearsonEducationInc.,publishingasBenjaminCummings(http://www.awbc.com)

**Itissuggestedthatyoucarefullylabeleachionchannelinthegraphicsinthissection.Ifthisisnotprintedin
color,youshouldalsocolorcodetheionchannelsandionsasfollows: Red:Sodiumionchannelsandsodiumions Blue:Potassiumionchannelsandpotassiumions Green:Chlorideionchannelsandchlorideions

Page 1. Introduction Gradients cause ions to move across cell membranes. This results in a separationofchargeacrossthemembrane,whichinturncreatesanelectrical potential,orforce. Theelectricalpotentialiscalledthemembranepotential. Page 2. Goals Toknowtherelativeconcentrationofionsinsideandoutsideofcells. Torecognizethatcellshaveselectivepermeabilityforions. Tounderstandtheequilibriumpotentialforpotassium. To understand that sodium and potassium determine the resting membrane potential. Torealizethat thesodiumpotassium pumpmaintainstheresting membrane potential. Page 3. The Concentration of Ions Differs Inside and Outside the Cell Fillinthischartasyouworkthrough thispage: Recallthattheintracellular concentrationsofsodium, potassium,andchloridedifferfrom theirconcentrationsoutsidethecell intheextracellularfluid. Insidethecell,theconcentrationof positivepotassiumionsishigh.Itis balancedbyahighconcentrationof negativelychargedproteinsand otheranions. Intheextracellularfluidoutsidethe cell,theconcentrationofpositive sodiumionsishigh.Itisbalanced byahighconcentrationofnegative chlorideions.

**Nowisagoodtimetogotoquizquestion1:
ClicktheQuizbuttonontheleftsideofthescreen.

Afteransweringquestion1,clicktheBacktoTopicbuttonontheleftsideofthescreen. Togetbacktowhereyouleftoff,clickonthescrollingpagelistatthetopofthescreenandchoose"4.Cells ExhibitSelectivePermeability".

Page 4. Cells Exhibit Selective Permeability Ionsarenotsolubleinthelipidbilayer;theycanonlycrosscellmembranesby passingthroughwateryporescalledionchannels. Ifacellhaschannelsforaparticularion,wesayitispermeabletothation. Sincemostcells arepermeable tosomeionsbutnottoothers, theyexhibit selectivepermeability. Thiscellmembraneisimpermeabletoions. This cell is permeable to potassium. Many cells in the body are selectively permeableonlytopotassium. Excitable cells are very permeable to potassium and slightly permeable to sodium. Neuronsareselectivelypermeabletopotassium,sodium,andchloride. Cellsareimpermeabletothenegativelychargedproteinsandotherlargeanions found inside them. These anions are too large to pass through the cell membrane. As you work through this page, color the potassium channels and thepotassiumionsblue, the sodium channels andthesodiumionsred, and the chloride channels and the chlorideionsgreen.

Page 5. Permeability Depends on the Number of Ion Channels Thepermeabilityofacellforaparticulariondependson: 1.Thenumberofchannelsforthation. Permeability canbeincreasedbyincreasingthenumberofchannelsfora givenion. 2.Theeasewithwhichtheioncanmovethroughthechannels.

Ifanionissmallcomparedtothesizeofanionchannel,itgoesthrough easily. Addingorremovingpotassiumionchannelstoacellwillchangethepermeabilityof thecelltopotassium.

Page 6. Permeability Can Change Rapidly When Gated Ion Channels are Opened Youhavelearnedthatsomechannelshavegatesthatmaybeeitheropenorclosed. Thepermeabilityofacellforagivenionincreaseswhengatedchannelsforthation areopened.Thisisthemechanismusedbythenervoussystemtoproducerapid changesinmembranepermeability.

Page 7. Potassium Diffuses Down Its Concentration Gradient Wearestudyingneurons.Butbeforewetalkabouthowionsmoveacrossneuronal cellmembranes,letstalkaboutasimplercell,onethatispermeabletoonlyone ion. Manyofthecellsofthebodyarelikethissimple,nonexcitablecell.Whenwe understandit,wewilllearnhowneuronsaredifferentbecausetheyarepermeable toseveralions. Thiscellisselectivelypermeableonlytopotassium. Gradientscauseionstomove.Potassiumwilldiffusedownitsconcentration gradientfromtheareawhereitsconcentrationishightotheareawhereits concentrationislow. Potassiumdiffusesoutofthecellfromitshighertolowerconcentration. Theconcentrationgradientactsasachemicalforcethatpushespotassiumoutof thecell.Thewidthofthearrowrepresentstherelativestrengthofthechemical force.

Indicatethedirectionofthechemical forceinanonexcitablecellwithan arrow. Colorcodetheionsandion channel:

Page 8. Diffusion of Potassium Out of The Cell Creates an Electrical Potential Across the Cell Membrane Aspotassiumionsdiffuseoutofthecell,theyaccumulateontheoutsidesurfaceof the cell membrane, making it more positive than the inside surface of the membrane.Thisresultsinaseparationofchargeacrossthecellmembrane. There is a net positive charge on the outside of the cell membrane, and a net negativechargeontheinside.

Thisseparationofchargecreatesanelectricalpotentialacrossthecellmembrane.

Page 9. The Electrical Potential Opposes Diffusion of Potassium Out of the Cell **Theconceptsonthispagearedifficult,butcrucialtoyourunderstanding.Spendtimewiththispageandplay
itoveragainasnecessarytofullyunderstandtheconcepts.

Imaginethatweputourcellinabathofextracellularfluidandwatchpotassium diffuse out. As potassium diffuses out, an electrical potential begins to develop. Since opposite charges attract each other, the developing electrical potential beginstopullpotassiumbackintothecell. Thus,theelectricalpotential,or voltage,actsasaforcethatopposesthediffusionofpotassiumoutofthecell. Thewidthofthearrowrepresentstherelativestrengthoftheelectricalforce. As potassium continues to diffuse down its concentration gradient, the developingelectricalpotential,orforce,increases. Potassiumwillcontinuetodiffuseoutuntiltheelectricalpotentialisequalbut oppositetotheforcefromtheconcentrationgradient. Two forces act on K+. Together these forces are called the Electrochemical Gradient. 1.TheConcentrationGradientorChemicalForce CausesK+todiffuseoutofthecell. 2.TheElectricalpotentialorElectricalforce PullsK+intothecell. Sincethechemicalandelectricalforcesonpotassiumareequalandopposite, therewillbenonetmovementofpotassiumacrossthemembrane.Potassium isatequilibrium. Labelthepartsofthisdiagram:

**Nowisagoodtimetogotoquizquestion3:
ClicktheQuizbuttonontheleftsideofthescreen. Clickonthescrollingpagelistatthetopofthescreenandchoose"3.ForcesonIons". Afteransweringquestion3,clicktheBacktoTopicbuttonontheleftsideofthescreen. Togetbacktowhereyouleftoff,clickonthescrollingpagelistatthetopofthescreenandchoose"10.The EquilibriumPotentialforPotassium.

Page 10. The Equilibrium Potential for Potassium The electrical potential across the cell membrane is called the membrane potential. Themembranepotentialismeasuredinmillivolts. Becausetheinsideofthecellisnegative,themembranepotentialisnegative. Aswe'veseen,asimplenonexcitablecellhasaconcentrationof150millimolar potassiuminsideand5millimolarpotassiumoutside.Attheseconcentrations, thechemicalandelectricalforcesonpotassiumareequalandoppositewhen themembranepotentialis90millivolts. Indicatethemembranepotentialhere:

Atthisspecialmembranepotential,potassiumisatequilibrium.Thisiscalled theequilibriumpotentialforpotassium.

**Nowisagoodtimetogotoquizquestion4:
ClicktheQuizbuttonontheleftsideofthescreen. Clickonthescrollingpagelistatthetopofthescreenandchoose"4.K +ConcentrationandtheMembrane Potential". Afteransweringquestion,clicktheBacktoTopicbuttonontheleftsideofthescreen. Togetbacktowhereyouleftoff,clickonthescrollingpagelistatthetopofthescreenandchoose"11.The ElectrochemicalGradientforSodiumDrivesitintotheCell".

Page 11. The Electrochemical Gradient for Sodium Drives it into the Cell Recallthatneuronsarepermeabletomorethanoneion. Let'sseehowthemembranepotentialinsuchcellsdiffersfromthemembrane potentialinsimplecellsthatarepermeableonlytopotassium. Whenneuronsarenotgeneratingelectricalsignals,wesaytheyareatrest. Restingneuronsareverypermeabletopotassium,andonlyslightlypermeableto sodium.Theyarealsopermeabletochloride,butsinceitcontributeslittleto therestingmembranepotential,wewillnotconsideritfurther. Wehaveobservedthemovementofpotassiumionsacrossaverypermeablecell membrane.Nowletsexaminemovementofsodium. Thewidthofthearrowrepresentstherelativestrengthofthechemicalforce. Youhavelearnedthatwhenpotassiumdiffusesoutofacellachargeseparation develops,producinganetnegativechargeinsidethecell.Neuronsarevery permeabletopotassium,sotheyhaveanetnegativechargeinsidetheir membrane. Sinceoppositechargesattracteachother,theelectricalpotentialresultingfrom thechargeseparationactsasaforcetopullsodiumintothecell. Thewidthofthearrowrepresentstherelativestrengthoftheelectricalforce. Theforcesfromtheconcentrationgradientandtheelectricalpotentialcombine toproducealargeelectrochemicalgradientforsodium. Thewidthofthearrowrepresentstherelativestrengthoftheelectrochemical gradient. Thiselectrochemicalgradientdrivessodiumintothecell. Labelthesediagrams:

Page 12. The Resting Membrane Potential in Neurons Depends on Sodium and Potassium

Inneuronsatrest,themembranepotentialiscalledtherestingmembrane potential. Ifaneuronwerepermeableonlytopotassium,itsrestingmembranepotential wouldbe90millivolts,theequilibriumpotentialforpotassium. However,restingneuronsarealsoslightlypermeabletosodium,andthe electrochemicalgradientforsodiumcausesittomoveintothecell. Therestingmembranepotentialresultsfromthemovementsofbothsodiumand potassiumions.Thepositivelychargedsodiumionsthathaveenteredthe neuronmakethemembranepotentialmorepositivethan90millivolts,which istheequilibriumpotentialforpotassium.Formanyneuronstheresting membranepotentialiscloseto70millivolts. Colorcodethisdiagramandrecordtherestingmembranepotentialforatypical neuron:

**Nowisagoodtimetogotoquizquestions2,6and7:
ClicktheQuizbuttonontheleftsideofthescreen. Clickonthescrollingpagelistatthetopofthescreenandchoose"2.IonChannelsinExcitableandNon excitableCells". Afteransweringquestion2,clicktheBacktoTopicbuttonontheleftsideofthescreen"6.TheSodium EquilibriumPotential". Workthroughquestions6and7. Afteransweringquestion7,clicktheBacktoTopicbuttonontheleftsideofthescreen. Togetbacktowhereyouleftoff,clickonthescrollingpagelistatthetopofthescreenandchoose"13. PotassiumLeaksOutoftheNeuronandSodiumLeaksIn".

Page 13. Potassium Leaks Out of the Neuron and Sodium Leaks In Whentherestingmembranepotentialisnotequaltothepotassiumequilibrium potential,theforcesactingonpotassiumarenolongerequalandopposite. At70millivolts,thechemicalforcepushingpotassiumoutofthecellisgreater thantheelectricalforcepullingpotassiumbackintotheneuron.Butonlya littlebit. Theforceonpotassiumissmall,buttheneuronisverypermeabletopotassium. Asaresult,asmallamountofpotassiummovescontinuouslyoutofthe neuron.

At70millivolts,theforceonsodiumisverylarge,buttheneuronisonly slightlypermeabletosodium.Asaresult,asmallamountofsodiummoves continuouslyintotheneuron. At70millivolts,therestingmembranepotential,potassiumleaksoutofthe neuron,andsodiumleaksintotheneuron. Colorcodethisdiagram.Usearrowstoindicatethedirectionofleakageof sodiumandpotassiumionsatrestingmembranepotential:

Page 14. The Neuron Must Compensate for Potassium and Sodium Leaks Justasaboatthatbeginstoleakwilleventuallysink,aleakingneuronwill eventuallyfailtofunction.Ifionscontinuetoleak,theneuronwillbeunableto communicate. Iftheionleakscontinue,theconcentrationgradientsforsodiumandpotassium willdecrease.Astheconcentrationgradientsdecrease,themembranepotential movestowardzero. Whentherearenolongeranychemicalorelectricalforcestomoveionsacross themembrane,theneuroncannotsendorreceivetheelectricalsignalsitneeds tocommunicate. Thecaptaincankeepherboatafloatbybailingwateroutasfastasitenters. Neuronscanpreventthepotassiumandsodiumgradientsfromrunningdown bytransportingpotassiumbackintothecellandsodiumbackoutofthecell. Page 15. The Sodium-Potassium Pump Maintains the Resting Membrane Potential Ofcourse,theneurondoesntusebucketstomoveions.Amembraneenzyme calledthesodiumpotassiumpumpactivelytransportsionstocompensatefor thesodiumandpotassiumleaks.

ThispumpusestheenergyofATPtomovesodiumandpotassiumagainsttheir electrochemicalgradients.Threesodiumionsarepumpedoutoftheneuron foreverytwopotassiumionsthatarepumpedin. Thepumpcompensatesforthesodiumandpotassiumleaks,keepingtheresting membranepotentialat70millivolts. Itisimportanttorememberthatthesodiumpotassiumpumpdoesnotcreate themembranepotential,itsjobistomaintainit. Inthefollowingdiagram,colorcodetheionchannelsandions.Usingarrows, showthedirectionofionsthrougheachoftheionchannels.

Page 16. Summary The concentrations of sodium and chloride are high outside cells in the extracellularfluid,andtheconcentrationsofpotassiumandorganicanionsare highinsidecells. The permeability of a cell for ions depends on the number and type of ion channelsinthecellmembrane. The electrical and chemical forces for a particular ion combine to become a singleforce,theelectrochemicalgradient,whichcausesthemovementofthat ionacrossthecellmembrane. In simple, nonexcitable cells, the membrane potential depends only on potassium. Potassiumcomestoequilibriumwhenthemembranepotentialforthecellis90 millivolts.

 The resting membrane potential in neurons depends on the distribution of sodium as well as potassium across the cell membrane. Resting membrane potentialsinneuronsarecommonlyaround70millivolts. Thesodiumpotassiumpumpisessentialformaintainingtherestingmembrane potentialinneurons. **Nowisagoodtimetogotoquizquestion5: ClicktheQuizbuttonontheleftsideofthescreen. Clickonthescrollingpagelistatthetopofthescreenandchoose"5.TheTruth aboutNeurons".

Notes on Quiz Questions: Quiz Question #1: Concentration of Ions This question asks you to predict the concentration of ions both inside and outsideaneuron. Quiz Question #2: Ion Channels in Excitable and Non-excitable Cells This question asks you to determine what ion channels are present in both excitableandnonexcitablecells.Italsoasksyoutodeterminewhichofthese ionchannelsareresponsiblefortherestingmembranepotentialineachcell type. Quiz Question #3: Forces on Ions This question asks you to define the electrochemical gradient, concentration gradient,andelectricalpotential. Quiz Question #4: K+ Concentration and the Membrane Potential Thisquestionasksyoutopredictwhathappenstothemembranepotentialifthe potassiumlevelsintheextracellularfluidincreasesordecreases. Quiz Question #5: The Truth about Neurons Thisquestionasksyoutodeterminewhichstatementaboutneuronsistrue. Quiz Question #6: Na+ Equilibrium Potential Thisquestionasksyoutodeterminetheequilibriumpotentialforsodium.Then youareaskedtodetermineifthereisanetmovementinoroutofthecellof sodiumandpotassiumionsatvariousmembranepotentials. Quiz Question #7: Permeability Changes Thisquestionasksyoutodeterminewhatwouldhappenifthereisasudden increaseinpermeabilityofsodiumorpotassium.

Study Questions on The Membrane Potential:

1.(Page3.)Whichoftheseionshaveahighconcentrationoutsidethecellandwhich haveahighconcentrationinsidethecell?Na+,K+,Cl 2.(Page4.)Whatistheonlywaythationscangetacrossthecellmembrane? 3.(Page4.)Whatdoesitmeantosaythatcellsexhibitselectivepermeabilitywith respecttoions. 4.(Page4.)Whichionaremostcellsinthebodypermeableto? 5.(Page4.)Howdoneuronsdifferfrommostoftheothercellsinthebodywithrespect toionpermeability? 6.(Page4.)What'sthedifferencebetweenaneuron'spermeabilitytosodiumand potassium? 7.(Page5.)Whattwofactorswillaffectthepermeabilityofacellforaparticularion? 8.(Page6.)Whatmechanismusedbythenervoussystemtoproducerapidchangesin membranepermeability? 9.(Page7.)Asopposedtoneurons,simple,nonexcitablecellsarepermeableonlytoone ion.Whatisthation? 10.(Page7.)Whatmajorfactorcausesionstomovethroughionchannels? 11.(Page7.)Whattypeofforceistheconcentrationgradient? 12.(Page8.)Howdoesthecellmembranebecomemorepositiveoutsideandmore negativeinside? 13.(Page8.)Whattypeofforceistheseparationofcharge? 14.(Page9.)Aspotassiumdiffusesoutofacell,theoutsideofthecellbecomesmore _______andtheinsideofthecellbecomesmore________.Sinceoppositecharges attracteachother,andpotassiumispositive,thepotassiumwill__________. 15.(Page9.)Theforcethatisresponsibleforthemovementofpositivepotassium ionsbackintothecell,whereitismorenegativeiscalledthe_________. 16.(Page9.)Whataretwoalternativenamesfortheelectricalforce?

17.(Page9.)Whatarethetwopartsoftheelectrochemicalgradient? 18.(Page9.)Whateffectdoesboththechemicalforceandtheelectricalforcehaveon K+?

19.(Page9.)WhenistherenonetmovementofK+acrossamembrane? 20.(Page9.)Whenthereisnonetmovement,doesthatmeanthationsarenotmoving acrossthemembrane? 21.(Page10.)Whatisamembranepotential? 22.(Page10.)Inwhatunitsisboththeconcentrationandthemembranepotential measured? 23.(Page10.)Whatistheequilibriumpotentialingeneral? 24.(Page10.)WhatistheequilibriumpotentialforK+inanonexcitablecell?What doesthismean? 25.(Page11.)Neuronsareslightlypermeabletosodiumions.a.Inwhichdirectionis thechemicalforceforsodium?Why?b.Inwhichdirectionistheelectricalforcefor sodium?Why? 26.(Page11.)Whatistheelectrochemicalgradientforsodiumacombinationof?In whichdirectionistheelectrochemicalgradientforsodium? 27.(Page12.)Whatdoestheterm"restingmembranepotential"inaneuronmean. Whatisatypicalvaluefortherestingmembranepotential. 28.(Page12.)Whydononexcitablecellshaveamembranepotentialof90mVwhile neuronshavearestingmembranepotentialof70mV? 29.(Page13.)At70millivolts,therestingmembranepotential,whydoespotassium leakoutoftheneuron? 30.(Page13.)At70millivolts,therestingmembranepotential,whydoessodium slowlyleakintotheneuron? 31.(Page15.)Whatcompensatesfortheleakageofsodiumandpotassiumions? 32.(Page15.)Doesthesodiumpotassiumpumpmovesodiumandpotassiumwith oragainsttheirgradients? 33.(Page15.)Whatprovidestheenergytopumpsodiumandpotassiumagainsttheir gradients? 34.(Page15.)Thesodiumpotassiumpumppumpsout______sodiumsforevery _____potassiumsthatarepumpedin.

35.(Page15.)Howdoesthesodiumpotassiumpumpkeeptherestingmembrane potentialat70millivolts. 36.(Page15.)Thesodiumpotassiumpump___________. a.createsthemembranepotential b.maintainsthemembranepotential