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Generalliterature

Bioelectricity:actionpotential

Principle

Asatypeofapropagatingdisturbanceofthenerve(ormuscle)membranepotentialtheelectrotonicpropagationhas
beendescribedinBioelectricity:electrotonicpropagation.Ithappensindendrites,axonsandmusclefibers.These
structurescanbesomemmlong,butaxonsandmusclefibersaremostlysomecmandaxonsmayreachmanymeters
(asinwhales).However,mostlyanelectrotonicpotentialisstronglyreducedalongdistancesofcentimeters,is
propagatingslowand,duetotemporalfiltering,thepeaktimeatthenerveterminalwillnotbeverywelldefined.Therefore
itisnotveryappropriatetotransmitinformationoverlongdistancesinlivingorganisms.Thereexistabetterwayof
propagatingnerveinformation.Thisisviaactionpotentials(spikes),anactivewayofpropagation.Withspikesinformation
transportisfaster,withhighertemporalresolutionandmoreinformationcanbetransmitted.Spikesarisefromthesomatic
potential,thesumofthedendriticpotentials,attheaxonhillockandthenpropagatealongaxons(sometimescertaintypes
ofdendrites),musclefibersandalsoheartmusclefibers.Fig.1visualizesthispropagation.

Fig.1Principleofpropagation.

Fig.2depictsthe3maintypes.Spiesarefoundinvertebratesandinvertebrates,butalsosomeplants(relyingonK+and
Ca++,withthephloemaschannels).

Fig.2Fromlefttorightactionpotentialofaxon,musclefiberandheartmusclecell.

Depolarizationandrepolarization
Belowtheaxonalspike,thecommononeisdescribed,firstforanunmyelinatedaxon.Fig.3givesthevariousphases
whichcanbedistinguishedduringitstimecoarse.Oftenonedendriticpotentialcangiverisetoacoupleofspikes,
dependingonitsamplitude.Apropagatingspikegenerallymaintainsitswaveformandamplitude.Thisiscausedbythe
factthatthemembraneconductancegm(=1/rm)oftheaxonisnotconstant.Anexcellentwaytoinvestigatethechanges
oftheconductancesisthevoltageclamptechnique(holdingthemembranepotentialataconstantvaluewhatever
injectedcurrentisneeded,seeElectrophysiology:clampingtechniques).Essentialforthistechniqueisthatthereflowsno
axialcurrentthroughtheaxon.Inathickaxon(squid),thisisachievedbyinsertingafinesilverwirelongitudinallyinan
axon.Byanintracellularelectrodeandanextracellularelectrodecurrentisinjectedintotheaxontocompensatefor
changesincurrentthroughthemembrane.Thecurrentneededintheclamptechniquecompensatestheioniccurrents
(andtheinitialcapacitivecurrent)andismeasuredasafunctionoftime.AccordingtoOhm'slawthetotalioniccurrentat
anytimeisproportionalwiththetotalmembraneconductancesincethemembranepotentialiskeptconstant.TheNa+
andK+conductancescanbemeasuredseparatelybyapplyingcertaindrugswhichmakeeithertheNa+ortheK+
conductancezero.TheNa+andK+havedifferenttypesofpores,i.e.selectivechannels.ThepermeabilityforNa+andK+
appearstobeafunctionofthemembranepotential.Inrest,mostNa+channelsareclosed,buttheK+channelsopen,
causingaconstantleakingoutofK+.ThisiswaytherestpotentialismainlydeterminedbyK+withits75timeshigher
conductivity.TheoutflowofK+isconstantlycompensatedbyNa+inflow.
Ifnowthemembraneisstimulatedandeitherdepolarizedorhyperpolarizedthemembranepotentialwillchangewith
time,resultingintimeandvoltagedependentionicresistances.NowrmiscomposedofaresistancerNa formedbythe
Na+channels,aresistancerKformedbytheK+channelsandrL formedbyotherpassiveionicchannels,mainlyforCl,
eachofthemconnectedwiththeNernstequilibriumpotential(seeBioelectricity).Thechannelmechanismsinvolvedin
thegenerationofaspikearetherapidincreaseinthepermeabilityforNa+andthedelayedandslowerincreaseinthe
permeabilityforK+ifthecellisdepolarized(socalledcathodalstimulation).Na+movesinundertheinfluenceofthe
drivingforce,thedifferencebetweenthemembranepotentialandtheequilibriumpotentialofNa+.Inthesquidaxonthis
occursinafewms.AssoonastheNa+permeability(orconductance)increases,moreNa+streamsintotheaxonor
soma,diminishingthemembranepotentialstillfurther.ThiscausesafurtherincreaseoftheNa+permeabilityandata
certaincriticalvalue,thefiringthreshold(about15mVmorepositivethanErest)thisbecomessostrongapositive

feedbackthatthecellevenreversesitspotentialtopositivevaluesinthedirectionoftheNa+equilibriumpotential.
Actually,thethresholdisreachedwhentheinwardNa+currentexceedstheoutwardK+current.Veryshortlyafterwards
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theNa+permeabilityreturnstoitsoriginalvalueandtheK+permeabilityincreasestemporarily.AswiththeNa+influx,itis
notthemovementofK+thatchangesE.ItisthevalueforgKrisingabovethatforgNa ,draggingEbacktowardsthe

equilibriumconstantforK+.SincethevoltagegatedK+channelshaveadelayedresponse,suchthatK+continuestoflow
outofthecellevenafterthemembranehasfullyrepolarized.Thiscausestheundershoot(shorthyperpolarization).
+
ThereisacommonmisconceptionthattheNa+/K pumprestorestherestingpotentialduringthespikefallingphaseby
activelypumpingNa+outandK+intotheneuron.This(alongwiththemisconceptionthatsodium'floods'thecelltocause
thespike),isnotcorrect.TheNa+/K+ATPase(thepump)doesultimatelymaintaintherestingpotentialbymaintainingthe
+
concentrationgradientsforNa+andK ,butdoessoonamuchslowertimescale.

Fig.3Basictimecoarseofactionpotential.

Refractoryperiod
Duringashortperiodaftertheoccurrenceofaspikethecellcannotbestimulated.Thisistherefractory(15ms)period
consistingofanabsoluteandrelativephase.Intheformer,theNa+channelscannotbeopenedbyastimulusirrespective
ofappliedvoltage.Inthesubsequentrelativephase,spikescanbeinitiated,sinceNa+channelsarereactivated(ina
stochasticmanner)butthethresholdisgreater.Thisiscausedbytheslightlyhyperpolarizedstateduetostillhigherthan
restingvalueforgK,somorevoltageisrequiredtoreachthreshold,andalsothethresholditselfishigherthanusual
becausesomeoftheNa+channelswillstillbeinactivated.(NotethatNa+channelhasatleastthreestates:closed,open
andinactivatedclosedandnotabletoopen).Therefractoryperiodisimportantbecauseitensuresunidirectional(one
way)propagationofthespike.
Thebasictheoryofspikepropagation,theHodgkinHuxley(HH)theory,isdescribedinMoreInfo.

Application

Spikes,mostlyintheformofspiketrains,areusedmostextensivelybythenervoussystemforcommunicationbetween
neuronsandfortransmittinginformationfromneuronstootherbodytissuessuchasmusclesandglands
(neurohypophysis).
Spikesaremeasuredwiththerecordingtechniquesofelectrophysiologyandmorerecentlywithneurochipscontaining
EOSFETs(electrolyteoxidesemiconductorfieldeffecttransistor).Suchchipsareappliedinretinalandcorticalimplants
torecordandstimulateneuronalactivity.(Acochlearimplantisformallynotaneurochipsinceitisonlyusedfor
stimulationitisaneuroprosthesis).Anoscilloscopeshowingthemembranepotentialrecordingfromasinglepointonan
axonshowseachstageofthespikeasthewavepasses.Aspeakerisveryusefultolistentotheelicitedspike(trains).

Spikesingeneralcannotbemeasuredatdistance,since,dueoitsdipolenature,itdiminisheswiththethirdpowerof
distance.Theelectrotonicpotentialchangescausedbysynaptictransmissionwhich,ifstrongenough,giverisetothe
spike,havealessstrongdecaywithdistance.Theyalsolastlonger.Ifthereisenoughgeometricalcoordinationbetween
agroupofexcitedneurons,socalledsloworgradedpotentialscanberecordedforinstanceontheskullofman.They
arealwayssignofmassaction.IftheyarespontaneouswespeakoftheEEG,iftheyareexcitedbylight,soundor
peripheralnervestimulationwespeakofvisual,auditoryorsomatosensoryevokedpotentials(EPs)respectively.Also
theelectroretinography(ERG)reflectsgradedpotentialsandnotthespikesoftheopticnerve.

Somediseasesreducethespeedofspikeconductance.Themostwellknownofthesediseasesismultiplesclerosis,in
whichthebreakdownofmyelinimpairscoordinatedmovement.

MoreInfo

TheconductancesforNa+andK+changeaccordingto:
gNa+=Na+m3 h,
gK+=K+n4 ,(1)
whereNa+andK+arethemaximalconductances.Thevariablesn,m,andhhaveavaluebetween0and1.Inthe

equationfortheK+conductancen4 denotesthefractionoftheK+channelswhichareopen.Ifallchannelsareopenthen
n4 n1.Ifallareclosedn=0.ApparentlyfoureventsofequalnaturehavetocoincidetoopenthefourfoldedlockedK+
channel.FortheNa+channeltwokindsofkeys(events)areused.Threeidenticalkeysareneededtoopenthethree
foldedmlock.Anotherlock(h)isopeninrest,butcloseswhenthemembraneisdepolarized.Thesefractionsm,handn
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arevoltageandconsequentlytimedependent.Theycanbefoundbysolvingthreeexperimentallyfounddifferential
equations.Fornthisequationis:
dn/dt=n (1n)n n(2a)
wheren denotestheopenconditionandn theclosedcondition.ThisisvisualizedinFig.4a.Aftersolving,n appears
tobeapositiveexponentialfunctionofthemembranepotentialEandn isanegativeone(Fig.4b1).Sinceduring
excitationEchangeswithtimethetwovariablesalsochangewithtimewhatfinallyresultsintheinitiallyprogressive
increaseofn4 ,forastepwisechangeofE(Fig.4c1).Fig.4c2givesthefinalvalueofnandn4 measuredduringvoltage
clamp.
ForNa+wehavetodowithachangeofmandh.Bothcanbecalculated.Thedifferentialequationsare:
dm/dt=m(1m)mmand(2b)
dh/dt=h (1h)h h.(2c)

Fig.4Thegatingmodelforpotassiumandsodium.b2)ande2)depictthedependencyofnandn4,andm,handhm3,whenavoltage
stepisappliedverylong(infinite).

Thetimecourseofmlookslikethatofnbutisfaster.However,hbehavesdifferently.Itdecreasesinsteadofincreases
duetothedecreaseofh andincreaseofh whenthemembraneisdepolarized(Fig.4e2).Therefore,alsoforlong

lastingdepolarization(voltageclamp)theNa+conductancerestorestoitsoriginallylowrestvaluewithinabout5ms(Fig.
4e2).Theoppositebehaviorofhandmduringlonglastingdepolarizationisclearlyshown.
ThecurrentswhichflowthroughthemembranearecomposedofthecapacitivecurrenticandthreeioniccurrentsofNa+

(throughthevariablegNa )ofK+(throughthevariablegK)andtheanioncurrent(mainlyCl,throughthefixedgI),together
ii.Fig.5givesthetimecoarseofaspike,togetherwithic,ii,theresumim,andalsotheunderlyinggKandgNa .Forthe4
composingcurrentstogethertherelationis(seeequation(2)and(3)ofBioelectricity:electrotonicpropagation):
im=(1/ra )2 E/x2 =cmE/t+n4 K(EEK)+m3 hNa (EENa )+L(EEL ).(3)

Fig.5Timecoarseofconductancesandcurrentsduringanactionpotential.AttimeAandBtheslopesoftheaction
potentialaremaximalandimzero.AtBbothreachtheirextrema.

Supposethatbysummationofdendriticandsomaticpotentialsattheaxonhillockaspikearises.Atthatsitethelocal
currentsbecomesostrongthatalsothenextpartofthe(axonal)membranebecomesenoughdepolarizedtobeexcited
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andapropagatedspikewithoutdecrementrunsalongtheaxon.Therefractoryperiodmakesthatthespikewillnot
reverseandoccuronlyonceforashortlastingstimulus.Ifanerveisstimulatedinthemiddleofanaxontheimpulsewill
propagatetobothsides.Longerlastingstimulimaycausetrainsofspikes.Justlikeforthepropagationofadendritic
potentialitcanbeshownthattheconductionvelocityisaparameteroftheequation:
2 d2 E/dt2 =cmdE/dt+n4 K(EEK)+m3 hNa (EENa )+L (EEL).(4)
Thenumericalsolutionofthisnonlineardifferentialequationgivesaquitecomplicatedexpressionof.
Spikesrecordedclosetothesoma(oraxonhillock)arebiphasic,astheoneofFig.3,butwhenrecordedinthevicinityof
anaxontheyaretriphasic.

OnecouldthinkthatanerveimpulsewhichreversesthenervepotentialwouldbringaboutanimportantdepletionofK+
whichleavesthecellbecausethereisnopotentialgradientanymorekeepingitintheinterior,andthattheinflowofNa+
wouldcauseapermanentdisturbanceofthemembranepotential.However,theamountsofionsdisplacedaresmall
comparedtotheactualnumberpresent.Eveninverysmallnervesseveralthousandsofspikescanbegeneratedwithout
asignificantlyincreasedmetabolismtoexpelNa+.

Thebehaviorofthechannelshasextensivelybeenstudiedbyclampingtechniques(seeElectrophysiology:clamping
techniques),inwhichthei/E(soconductance)isinfluencedbyadministratingallkindofdrugs.Adiscussionofthese
phenomenaisbeyondthescopeofthischapter.

Myelinatedaxons
Propagationspeedcanbeincreasedbyincreasingtheaxondiameter.Takingforsimplicityequation(8)of
Bioelectricity:electrotonicpropagation(=2/=0.5Cm1 (d/(RmRi))0.5 )thisspeedisproportionalwiththesquareroot
ofdiameter(d).
However,formetabolicreasons,thediameterislimited(onlythecoldbloodedsquidreachesavalueof1mm).
Unmyelinatedfibers(about2m)aregenerallyfoundintheautonomicnervoussystemofvertebrateswherespeedsof
about1m/saresufficient.
Invertebrates,sensoryandmotoronesaregenerallymyelinated.Thisismoreeffectivetoincrease.Theeffectofmyelin
canalsobeevaluatedsinceallaboveconsiderationscanbeappliedinprincipletothemyelinatednerve.Myelincanbe
consideredasthedielectricumbetweentwocondenserplates.Itdecreasesmembranecapacitance,sincemyelinhasa
lowerrelativedielectricconstantm(about718)thaninterstitialfluid(mclosetomofwater,beingabout80Cm~m/d).

Now,Cmisonlyabout4nF/cm2 .andRmisabout105 cm2 .Increasingtheeffectivemembranethicknessbyusingmyelin

(leavingtheinnerfiberdiameterconstant)alsodecreasesCm,so.Whenmyelinthicknessandinnerdiameterincrease
withthesamefactor,thenincreaseslinearwiththisfactorasfollowsfrom(5).Thisshowstheefficiencyofdiameter
increase.Experimentallythishasbeenfoundindeedforvertebrateperipheralfibers.
However,amyelinatedfiberlongerthansome100mdoesnotworkproperly.Myelinallowstherapid(essentially
instantaneous)conductionofions,butpreventstheregenerationofspikes.Therefore,thecylindricalshapeofthemyelin
sheathisinterruptedevery0.010.1mmbyanodeofRanvier,anakedpieceofca.0.5mofaxon.TheirCmisabout4

F/cm2 andRmisonlyabout15cm2 .AnabundanceofvoltagegatedNa+channelsonthesebaresegments(upto104

morethantheirdensityinunmyelinatedaxons)allowsspikestobeefficientlyregeneratedatthenodesofRanvier.The
excitationjumpsfromonenodetotheother,whichisapassive,soelectrotonictransmission(seeBioelectricity:
electrotonicpropagation)implyingsomedecrement.Basically,thiscangoineitherdirections,butthespiketravels
unidirectionalbecausethenodebehindthepropagatingspikeisrefractory.Thiswayofpropagationofthespikeiscalled
saltatoryconduction:atthemyelinatedsegmentsthepropagationisveryfast(duetotheinsulation),whereasatthenodes
thereisasmalldelayof0.01to0.1ms.Thelengthoftheinternodalsegmentsaresuchthatone,orsometimeseventwo
nodescanbepassedandthattheamplitudeisstillsufficienttoreachthethresholdforrestoringtheamplitudeofthe
spike.Thus,thesafetyfactorofsaltatoryconductionishigh,allowingtransmissiontobypassnodesincaseofinjury.
Mammalianmyelinatedmotorneuronscanreach100m/s.Saltatoryconductionincreasesnerveconductionvelocity
withouthavingtodramaticallyincreaseaxondiameter.Withoutsaltatoryconduction,conductionvelocitywouldneed
largeincreasesinaxondiameter,resultinginorganismswithnervoussystemstoolargefortheirbodies.

Alternativemodels
Afewobservationsarenoteasilyreconciledwiththemodel.Asignaltravelingalonganeuronisaccompaniedbyaslight
localthickeningofthemembraneandaforceactingoutwards.
Also,aspiketravelingalonganeuronresultsinaslightincreaseintemperaturefollowedbyadecreaseintemperature,
whereaselectricalchargestravelingthrougharesistoralwaysproduceheat.
TherecentsolitonmodelexplainstheaboveobservationsandpossiblyallpropertiesoftheHHmodel.Asolitonisaself
reinforcingsolitarywave(awavepacketorpulse)thatmaintainsitsshapewhileittravelsatconstantspeedsolitonsare
causedbyacancelationofnonlinearanddispersiveeffectsinthemedium.Thistheoryattemptstoexplainsignalsin
neuronsaspressure(orsound)solitonstravelingalongthemembrane,accompaniedbyelectricalfieldchangesresulting
fromPiezoelectricity.

Literature
HHmodel:
Noble,Physiol.Review,46,150,1966.
Solitonmodel:
HeimburgT,JacksonAD.Onsolitonpropagationinbiomembranesandnerves.PNAS,102,122005.
HeimburgT,JacksonAD.Thethermodynamicsofgeneralanesthesia.BiophysicalJournal,9,February2007.
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