复旦生理学课件02细胞的兴奋

•chap.2Therestingmembranepotential•chap.3Actionpotential第二章细胞的兴奋fromBerne&LevyPrinciplesofPhysiology(4thed)2005•chap.16Electricalactivityoftheheart•chap.17NaturalexcitationoftheheartObservationsofMembranePotentials4.ACTIONPONTIELS1.IONICEQUILIBRIA2.RESTINGMEMBRANEPOTENTIALS3.SUBTHRESHOLDRESPONSES5.心肌细胞和起搏细胞的动作电位ObservationsofMembranePotentials•Extracellularrecording•Intracellularrecording•Voltageclampmacroscopicalcurrent•Patchclampsinglechannelcurrent1.IONICEQUILIBRIAConcentrationforceElectricalforceElectrochemicalEquilibrium•Whentheforcecausedbytheconcentrationdifferenceandtheforcecausedbytheelectricalpotentialdifferenceareequalandopposite,nonetmovementoftheionoccurs,andtheionissaidtobeinelectrochemicalequilibriumacrossthemembrane.•Whenanionisinelectrochemicalequilibrium,theelectrochemicalpotentialdifferenceiscalledasequilibriumpotentialorNernstpotential.TheNernstEquationBABAXXXzFRTEEE][][lnWhereEXequilibriumpotentialofX+RidealgasconstantTabsolutetemperaturezchargenumberoftheionFFaraday’snumbernaturallogarithmofconcentrationrationofX+onthetwosidesofthemembraneBAXX][][ln•AtanymembranepotentialotherthantheEx,therewillbeanelectrochemicaldrivingforceforthemovementofX+acrossthemembrane,whichtendtopullthemembranepotentialtowarditsEX.•ThegreaterthedifferencebetweenthemembranepotentialandtheEXwillresultinagreaterdrivingforcefornetmovementofions.•Movementcanonlyhappenifthereareopenchannels!DistributionofIonsAcrossPlasmaMembranesofahumanskeletalmusclecell2.RESTINGMEMBRANEPOTENTIALSThecytoplasmisusuallyelectricallynegativerelativetotheextracellularfluid.Thiselectricalpotentialdifferenceacrosstheplasmamembraneinarestingcelliscalledtherestingmembranepotential.TheChordConductanceEquationClClNaNaKKmEggEggEggEwhereEmmembranepotentialEsequilibriumpotentialsoftheionsgsconductanceofthemembranetotheions.themorepermeable,thegreatertheconductance.ClNaKgggg•TheNa+,K+-ATPasecontributesdirectlytogenerationoftherestingmembranepotential.•Alltheionsthatthemembraneispermeabletocontributetotheestablishmentofthepotentialofthemembraneatrest.•细胞膜在静息状态下对K+的通透性一般大于其它离子（主要是IK1），因此大多数细胞的静息膜电位都是胞内为负。3.SUBTHRESHOLDRESPONSES•Thesize(amplitude)ofthesubthresholdpotentialisdirectlyproportionaltothestrengthofthetriggeringevent.•Asubthresholdpotentialcanbeeitherhyperpolarizing(makemembranepotentialmorenegative)ordepolarizing(makemembranepotentialmorepositive)gradedpotential•Thispassivespreadofelectricalsignalswithnochangesinmembranepropertyisknownaselectrotonicconduction.•Subthresholdpotentialsdecreaseinstrengthastheyspreadfromtheirpointoforigin,i.e.conductedwithdecrement.localresponsespatialsummation&temporalsummation4.ACTIONPONTIELSAnactionpotentialisarapidchangeinthemembranepotentialfollowedbyareturntotherestingmembranepotential.actionpotentialofasquidgiantaxon•Atpeakofactionpotentialmembranepotentialreversesfromnegativetopositive(overshoot).•Duringthehyperpolarizingafterpotential,themembranepotentialactuallybecomeslessnegativethanitisatrest.•Risingphase(depolarizationphase)•Repolarizationphase•Anactionpotentialistriggeredwhenthedepolarizationissufficientforthemembranepotentialtoreachathreshold.IonicMechanismsofActionPotentialKmKKEEIgNamNaNaEEIgchangesofionconductanceduringactionpotential•Actionpotentialsariseasaresultofbriefalterationsintheelectricalpropertiesofthemembrane.•Duringtheearlypartoftheactionpotential,therapidincreaseingNacausesthemembranepotentialtomovetowardENa.•TherapidreturnoftheactionpotentialtowardtherestingpotentialiscausedbytherapiddecreaseingNaandthecontinuedincreaseingK.•Actionpotentialsdifferinsizeandshapeindifferentcells,butthefundamentalmechanismsunderlyingtheinitiationofthesepotentialsdoesnotvary.•Duringthehyperpolarizingafterpotential,whenthemembranepotentialisactuallymorenegativethantherestingpotential,gNareturnstobaselinelevels,butgKremainselevatedaboverestinglevels.modelofthevoltage-dependentNa+channelclosedopeninactivated•去极相：INa激活，钠内流枪乌贼巨轴突动作电位各个时期的主要电流•超级化后电位：膜电位复极到静息电位时，IK仍然开放，钾继续外流使得膜电位超级化；随着IK的缓慢关闭，膜电位逐渐回到静息电位。•复极相：INa失活；IK激活，钾外流•Eitherastimulusfailstoelicitanactionpotentialoritproducesafull-sizedactionpotential.PropertiesofActionPotentialAll-or-NoneResponse•Thesizeandshapeofanactionpotentialremainthesameasthepotentialtravelsalongthecell.•Theintensityofastimulusisencodedbythefrequencyofactionpotentials.RefractoryPeriodrelativerefractoryperiodabsoluterefractoryperiodConductionofActionPotentialLocalcircuitcurrentSelf-reinforcing•myelinationConductionvelocity•diametersaltatoryconduction5.细胞动作电位的多态性心脏中两种细胞的动作电位心肌细胞起搏细胞心肌细胞动作电位的波形4期：静息期•0期：快速去极化期-90mVto+30mV,1~2ms•1期：快速复极化初期+30mVto0mV,10ms•2期：平台期0mV,100~150ms•3期：快速复极化末期0mVto-90mV,100~150ms心肌细胞动作电位的离子机制心肌细胞动作电位不同时期的主要离子通道IK1：内向整流钾通道•INa：快钠通道激活和失活的速率很快•Ica,L：L型钙通道激活电位约-30mV，激活速度较慢（约20ms），失活速度很慢（约500ms）•Ito：瞬时外向钾通道激活（约2ms）和失活（20ms）都相对较快•IK：延迟整流钾通道缓慢激活和失活（200~1000ms），激活后电流随膜电位呈现整流性质心肌细胞动作电位各个时期的主要电流•1期：快速复极化初期INa失活；Ito激活，钾外流•0期：快速去极化期INa激活，钠内流•3期：快速复极化末期Ica,L逐渐失活，IK进一步激活，钾外流•4期：静息期IK关闭；IK1电流增强•2期：平台期Ito失活；IK1通透性降低；IK和Ica,L激活，钾外流和钙内流相当IK1的