北大神经生物学3离子通道和神经元的电活动ppt课件

NeuronalElectricActivities神经元的电活动 NeuronalElectricActivitiesInclude RestPotential Chapter3 ActionPotential Chapter4 LocalPotentialsPost SynapticPotentialExcitatoryPost SynapticPotentialInhibitoryPost SynapticPotentialEnd platePotentialReceptorPotential Chapter3TheNeuronalMembraneatRest TheCASTOFCHEMICALSCytosolandExtracellularFluidThePhospholipidMembraneProteinTheMOVEMENTOFIONSDiffusionElectricityTheIONICBASISOFRESTINGMEMBRANEPOTENTIALEquilibriumPotentialTheDistributionofIonsAcrosstheMembraneRelativeIonPermeabilitiesofMembraneatRestTheImportanceofRegulatingtheExternalPotassiumConcentrationCONCLUDINGREMARKS CytosolandExtracellularFluid Water Itsunevendistributionofelectricalcharge soH2OisapolarmoleculeIons Saltdissolvesreadilyinwaterbecausethechargedportionsofthewatermoleculehaveastrongerattractionfortheionsthantheyhaveforeachother ThePhospholipidMembrane 磷脂膜 Thelipidsoftheneuronalmembraneforming abarriertowater solubleionsabarriertowater 头端 极性磷酸盐 亲水 尾端 非极性碳氢化合物 疏水 5 Protein Theseproteinsprovideroutesforionstocrosstheneuronalmembrane Therestingandactionpotentialsdependonspecialproteinsthatspanthephospholipidbilayer Protein AminoAcids ThePeptideBond 肽键 andaPolypeptide 多肽 Figure3 6ProteinStructure Theprimarystructure Thesecondarystructure Thetertiarystructure Thequaternarystructure Eachofthedifferentpolypeptidescontributingtoaproteinwithquaternarystructureiscalledasubunit 亚基 ChannelProteins Channelproteinissuspendedinaphospholipidbilayer withitshydrophobic 疏水的 portioninsidethemembranehydrophilic 亲水的 endsexposedtothewateryenvironmentsoneitherside Figure3 7AMembraneIonChannel 10 TwoPropertiesofIonChannels Ionselectivity 离子选择性 ThediameteroftheporeThenatureoftheRgroupsliningitGating 门控特性 Channelswiththispropertycanbeopenedandclosed gatedbychangesinthelocalmicroenvironmentofthemembrane IonPumps 离子泵 IonpumpsareenzymesthatusetheenergyreleasedbythebreakdownofATPtotransportcertainionsacrossthemembrane Chapter3TheNeuronalMembraneatRest THECASTOFCHEMICALSCytosolandExtracellularFluidThePhospholipidMembraneProteinTHEMOVEMENTOFIONSDiffusionElectricityTHEIONICBASISOFRESTINGMEMBRANEPOTENTIALEquilibriumPotentialTheDistributionofIonsAcrosstheMembraneRelativeIonPermeabilitiesofMembraneatRestTheImportanceofRegulatingtheExternalPotassiumConcentrationCONCLUDINGREMARKS THEMOVEMENTOFIONS Achannelacrossamembraneislikeabridgeacrossariver Anopenchannel Anetmovementofionsacrossthemembrane Ionmovementrequiresthatexternalforcesbeappliedtodriveionsacross Twofactorsinfluenceionmovementthroughchannels Diffusion 扩散 Electricity 电势差 Diffusion Temperature dependentrandommovementofionsandmoleculestendstodistributetheionsevenlythroughoutthesolutionsothatthereisanetmovementofionsfromregionsofhighconcentrationtoregionsoflowconcentration Thismovementiscalleddiffusion 扩散 Adifferenceinconcentrationiscalledaconcentrationgradient 浓度梯度 15 Figure3 8Diffusion DrivingionsacrossthemembranebydiffusionhappenswhenThemembranepossesseschannelspermeabletotheionsThereisaconcentrationgradientacrossthemembrane Electricity Anotherwaytoinduceanetmovementofionsinasolutionistouseanelectricalfield 电场 becauseionsareelectricallychargedparticles Oppositechargesattractandlikechargesrepel Figure3 9Themovementofionsinfluencedbyanelectricalfield Oppositechargesattractandlikechargesrepel Electricity Twoimportantfactorsdeterminehowmuchcurrent I willflow Electricalpotential V 电势 Electricalconductance g 电导 ElectricalconductanceElectricalresistance 电阻 R 1 g Ohm slaw I gV Figure3 10Electricalcurrentflowacrossamembrane DrivinganionacrossthemembraneelectricallyrequiresThemembranepossesseschannelspermeabletotheionsThereisaelectricalpotentialdifferenceacrossthemembrane 20 DiffusionandElectricity Electricalchargedionsinsolutiononeithersideoftheneuronalmembrane 带电离子溶解在细胞膜两侧的溶液中 Ionscancrossthemembraneonlybyproteinchannel 离子必须通过离子通道实现跨膜运动 Theproteinchannelscanbehighlyselectiveforspecificions 离子通道对离子具有高度的选择性 Themovementofanyionthroughchanneldependsontheconcentrationgradientandthedifferenceinelectricalpotentialacrossthemembrane 离子的跨膜运动依赖于膜两侧的浓度梯度和电位差 Chapter3TheNeuronalMembraneatRest TheCASTOFCHEMICALSCytosolandExtracellularFluidThePhospholipidMembraneProteinTheMOVEMENTOFIONSDiffusionElectricityTheIONICBASISOFRESTINGMEMBRANEPOTENTIALEquilibriumPotentialTheDistributionofIonsAcrosstheMembraneRelativeIonPermeabilitiesofMembraneatRestTheImportanceofRegulatingtheExternalPotassiumConcentrationCONCLUDINGREMARKS Themembranepotential 膜电位 isthevoltageacrosstheneuronalmembraneatanymoment representedbythesymbolmV Microelectrode 微电极 andmVmeasurement THEIONICBASISOFTHERESTINGMEMBRANEPOTENTIAL 静息电位 EstablishingEquilibriumPotential 平衡电位 Figure3 12Establishingequilibriuminaselectivelypermeablemembrane NopotentialdifferenceVm 0mV Thediffusionalforce TheelectricalforceVm 80mV 20 1 Equilibriumpotentials Theelectricalpotentialdifferencethatexactlybalancesanionicconcentrationgradientiscalledanionicequilibriumpotential orsimplyequilibriumpotential 当离子移动所产生的电位差和离子移动所造成的浓度势能差平衡时 不再有离子的净移动 这时膜两侧的电位差称为离子的平衡电位 GeneratingasteadyelectricalpotentialdifferenceacrossamembranerequiresAnionicconcentrationgradientSelectiveionicpermeability 25 Beforemovingontothesituationinrealneurons fourimportantpointsshouldbemade Largechangesinmembranepotentialarecausedbyminusculechangesinionicconcentrations 仅需要微小的离子浓度改变就可以引起膜电位大幅度的变化 100mM 99 99999mM Vm 80mV Vm 0mV Beforemovingontothesituationinrealneurons fourimportantpointsshouldbemade 2 Thenetdifferenceinelectricalchargeoccursattheinsideandoutsidesurfacesofthemembrane 膜内外两侧电荷的不同仅仅分布于膜的内外侧面 而不是分布于整个细胞的内外液 Figure3 13 5nm Beforemovingontothesituationinrealneurons fourimportantpointsshouldbemade Ionsaredrivenacrossthemembraneatarateproportionaltothedifferencebetweenthemembranepotentialandtheequilibriumpotential 离子的跨膜速率与膜电位和平衡电位的差值成正比 NetmovementofK occursasthemembranepotentialdifferedfromtheequilibriumpotential Thisdifference Vm Eion iscalledtheionicdrivingforce 离子驱动力 Iftheconcentrationdifferenceacrossthemembraneisknownforanion anequilibriumpotentialcanbecalculatedforthation 根据某离子膜两侧浓度的差值可以计算该离子的平衡电位 Na EquilibriumPotential Figure3 14Anotherexampleestablishingequilibriuminaselectivelypermeablemembrane TheNernstEquation TheexactvalueofanequilibriumpotentialinmVcanbecalculatedusingtheNernstequation whichtakesintoconsideration ThechargeoftheionThetemperatureTheratiooftheexternalandinternalionconcentrationsPage64 Box3 2 MarkF Bear etal ed Neuroscience ExploringtheBrain 2ndedition EK 2 303log 30 Figure3 15 Figure3 15Approximateionconcentrationsoneithersideofaneuronalmembrane RelativeIonPermeabilitiesofMembraneatRest TherestingmembranepermeabilityisfortytimesgreatertoK thantoNa Therestingmembranepotentialis 65mV TheDistributionofIonsAcrosstheMembrane Ionicconcentrationgradientsareestablishedbytheactionsofionspumpsintheneuronalmembrane 膜内外两侧的离子浓度梯度的形成依赖于离子泵的活动 Twoimportantionpumps Thesodium potassiumpump 钠钾泵 isanenzymethatbreaksdownATPinthepresenceofinternalNa Thecalciumpump 钙泵 isanenzymethatactivelytransportsCa2 outofthecytosolacrossthecellmembrane Figure3 16 Figure3 16Thesodium potassiumpump K K Na Na Figure4 4 Membranecurrentsandconductances 35 ThemostpotassiumchannelshavefoursubunitsthatarearrangedlikethestavesofabarreltoformaporeOfparticularinterestisaregioncalledtheporeloop 孔袢 whichcontributestotheselectivityfilterthatmakesthechannelpermeablemostlytoK ions Thewideworldofpotassiumchannels Figure3 18 Figure3 18Aviewoftheatomicstructureofthepotassiumchannelpore Theimportanceofregulatingtheexternalpotassiumconcentration Increasingextracellularpotassiumdepolarizesneurons Figure3 19Thedependenceofmembranepotentialonexternalpotassiumconcentration Twoprotectivemechanismsinthebrain Blood brainbarrier 血脑屏障 limitsthemovementofpotassium andotherblood bornesubstances intotheextracellularfluidofthebrainGlia particularlyastrocytes takeupextracellularK wheneverconcentrationsrise astheynormallydoduringperiodsofneuralactivity Figure3 20 Figure3 20Potassiumspatialbufferingbyastrocytes Whenbrain K oincreasesasaresultoflocalneuralactivity K entersastrocytesviamembranechannels TheextensivenetworkofastrocyticprocesseshelpsdissipatetheK overalargearea 40 Chapter3TheNeuronalMembraneatRest TheCASTOFCHEMICALSCytosolandExtracellularFluidThePhospholipidMembraneProteinTheMOVEMENTOFIONSDiffusionElectricityTheIONICBASISOFRESTINGMEMBRANEPOTENTIALEquilibriumPotentialTheDistributionofIonsAcrosstheMembraneRelativeIonPermeabilitiesofMembraneatRestTheImportanceofRegulatingtheExternalPotassiumConcentrationCONCLUDINGREMARKS NeuronalElectricActivitiesInclude RestPotential Chapter3 ActionPotential Chapter4 LocalPotentialsPost SynapticPotentialExcitatoryPost SynapticPotentialInhibitoryPost SynapticPotentialEnd platePotentialReceptorPotential Chapter4TheActionPotential PROPERTIESOFTHEACTIONPOTENTIALTheUpsandDownsofanActionPotentialsGenerationofanActionPotentialTheGenerationofMultipleActionPotentialsTHEACTIONPOTENTIALINTHEORYMembraneCurrentsandConductancesTheInsandOutsofActionPotentialTHEACTIONPOTENTIALINREALITYTheVoltage GatedSodiumChannelVoltage GatedPotassiumChannelsPuttingthePiecesTogetherACTIONPOTENTIALCONDUCTIONFactorinfluencingconductionvelocityACTIONPOTENTIALS AXONS ANDDENDRITESCONCLUDINGREMARKS MethodsofRecordingActionPotentials 细胞内记录 细胞外记录 示波器 TheUpsandDownsofanActionPotentials 65mV 45 Generationofanactionpotential Theperceptionofsharppainwhenathumbtackentersyourfootiscausedbythegenerationofactionpotentialsincertainnervefibersintheskin Thethumbtackenterstheskin 图钉扎入皮肤 Themembraneofthenervefibersintheskinisstretched 感觉神经纤维的细胞膜被牵拉 Na permeablechannelsopen TheentryofNa depolarizesthemembrane Na 通道打开 细胞膜产生去极化 Thecriticallevelofdepolarizationthatmustbecrossedinordertotriggeranactionpotentialiscalledthreshold 阈电位 Actionpotentialarecausedbydepolarizationofthemembranebeyondthreshold Thedepolarizationthatcausesactionpotentialarisesindifferentwaysindifferentneurons 引起去极化的不同方式 CausedbytheentryofNa throughspecializedionchannelsthatsensitivetomembranestretching 膜的牵拉 Ininterneurons depolarizationisusuallycausedbyNa entrythroughchannelsthataresensitivetoneurotransmitters 神经递质的释放 releasedbyotherneurons3 Inadditiontothesenaturalroutes neuronscanbedepolarizedbyinjectingelectricalcurrent 注入电流 throughamicroelectrode amethodcommonlyusedbyneuroscientiststostudyactionpotentialsindifferentcells Applyingincreasingdepolarizationtoaneuronhasnoeffectuntilitcrossesthreshold andthen pop oneactionpotential Forthisreason actionpotentialsaresaidtobe all or none 全或无现象 Thegenerationofmultipleactionpotentials ContinuousdepolarizingcurrentManyactionpotentialsinsuccession 注入电流 Thefiringfrequencyofactionpotentialsreflectsthemagnitudeofthedepolarizingcurrent 频率反应去极化电流的大小 Thisisonewaythatstimulationintensityisencodedinthenervoussystem 中枢神经系统编码刺激强度的一种方式 Thoughfiringfrequencyincreaseswiththeamountofdepolarizingcurrent thereisalimittotherateatwhichaneuroncangenerateactionpotentials Absoluterefractoryperiod 绝对不应期 Onceanactionpotentialisinitiated itisimpossibletoinitiateanotherforabout1ms 动作电位产生后1ms 不可能产生别的动作电位 Relativerefractoryperiod 相对不应期 Theamountofcurrentrequiredtodepolarizetheneurontoactionpotentialthresholdiselevatedabovenormal 绝对不应期之后的几个ms 需要比正常更大的阈电流才能爆发动作电位 50 Chapter4TheActionPotential PROPERTIESOFTHEACTIONPOTENTIALTheUpsandDownsofanActionPotentialsGenerationofanActionPotentialTheGenerationofMultipleActionPotentialsTHEACTIONPOTENTIALINTHEORYMembraneCurrentsandConductancesTheInsandOutsofActionPotentialTHEACTIONPOTENTIALINREALITYTheVoltage GatedSodiumChannelVoltage GatedPotassiumChannelsPuttingthePiecesTogetherACTIONPOTENTIALCONDUCTIONFactorinfluencingconductionvelocityACTIONPOTENTIALS AXONS ANDDENDRITESCONCLUDINGREMARKS THEACTIONPOTENTIALINTHEORY Depolarizationofthecellduringtheactionpotentialiscausedbytheinfluxofsodiumionsacrossthemembrane 去极化是钠离子内流造成的 Repolarizationiscausedbytheeffluxofpotassiumions 复极化是钾离子外流造成的 TheInsandOutsofActionPotential TherisingphaseAverylargedrivingforceonNa 80 62 mV 142mVThemembranepermeabilitytoNa K Depolarizationofthemembranebeyondthreshold membranesodiumchannelsopened ThiswouldallowNa toentertheneuron causingamassivedepolarizationuntilthemembranepotentialapproachedENa ThefallingphaseThedominantmembraneionpermeabilitytoK K flowoutofthecelluntilthemembranepotentialapproachedEK Theinsandoutsandupsanddownsoftheactionpotentialinanidealneuronisshownasbelow Fig4 5 55 Chapter4TheActionPotential PROPERTIESOFTHEACTIONPOTENTIALTheUpsandDownsofanActionPotentialsGenerationofanActionPotentialTheGenerationofMultipleActionPotentialsTHEACTIONPOTENTIALINTHEORYMembraneCurrentsandConductancesTheInsandOutsofActionPotentialTHEACTIONPOTENTIALINREALITYTheVoltage GatedSodiumChannelVoltage GatedPotassiumChannelsPuttingthePiecesTogetherACTIONPOTENTIALCONDUCTIONFactorinfluencingconductionvelocityACTIONPOTENTIALS AXONS ANDDENDRITESCONCLUDINGREMARKS Voltageclamp 电压钳 provestheabovetheory TheVoltage GatedSodiumChannel 电压门控的钠离子通道 TheproteinformsaporeinthemembranethatishighlyselectivetoNa ions 对Na 具有高度的选择性 Theporeisopenedandclosedbychangesintheelectricalpotentialofthemembrane Na 通道的开放和关闭具有电压依从性 Sodiumchannelstructure Na 通道的结构 CreatedfromasinglelongpolypeptideHas4distinctdomains numberedI IV ThefourdomainsarebelievedtoclumptogethertoformaporebetweenthemEachdomainconsistsof6transmembranealphahelices numberedS1 S6Thechannelhasporeloopsthatareassembledintoaselectivityfilter 60 Figure4 6Structureofthevoltage gatedsodiumchannel a Howthesodiumchannelpolypeptidechainisbelievedtobewovenintothemembrane Themoleculeconsistsoffourdomains I IV Eachdomainconsistsof6alphahelices whichpassbackandforthacrossthemembrane Figure4 6 b AnexpandedviewofonedomainshowingthevoltagesensorofalphahelixS4andtheporeloop red whichcontributestotheselectivityfilter c Aviewofthemoleculeshowinghowthedomainsmayarrangethemselvestoformaporebetweenthem 电压感受器 Figure4 7 Whenthemembraneisdepolarizedtothreshold themoleculetwistsintoaconfigurationthatallowsthepassageofNa throughthepore ThevoltagesensorresidesinsegmentS4ofthemolecule Inthissegment positivelychargedaminoacidresiduesareregularlyspacedalongthecoilsofthehelix Thus theentiresegmentcanbeforcedtomovebychangingthemembranepotential DepolarizationpushesS4awayfromtheinsideofthemembrane andthisconformationalchangeinthemoleculecausesthegatetoopen Thepatch clamp 膜片钳 Method 40mV 65 Functionalpropertiesofthesodiumchannel Na 通道的功能 TheyopenwithlittledelayTheystayopenforabout1msandthenclose inactivate Theycannotbeopenedagainbydepolarizationuntilthemembranepotentialreturnsto 65mV 关闭 开放 失活 去失活 Functionalpropertiesofthesodiumchannel Figure4 9 c Amodelforhowchangesintheconformationofthesodiumchannelproteinmightyielditsfunctionalproperties Theclosed 关闭 channel Opens 开放 uponmembranedepolarization Inactivation 失活 occurswhenaglobularportionoftheproteinswingsupandoccludesthepore Deinactivation 去失活 occurswhentheglobularportionswingsawayandtheporeclosesbymovementofthetransmembranedomains 关闭 开放 失活 去失活 Toxinsonthesodiumchannel Tetrodotoxin TTX 河豚毒素 andsaxitoxinChannel blockingtoxinBatrachotoxin veratridineandaconitineOpenthechannelsinappropriatelyOpenatmorenegativepotentialsOpenmuchlongerthanusual PuttingthePiecesTogether page89 ThresholdRisingphaseOvershootFallingphaseUndershootAbsoluterefractoryperiodRelativerefractoryperiod Figure4 10Themolecularbasisoftheactionpotential 70 Chapter4TheActionPotential PROPERTIESOFTHEACTIONPOTENTIALTheUpsandDownsofanActionPotentialsGenerationofanActionPotentialTheGenerationofMultipleActionPotentialsTHEACTIONPOTENTIALINTHEORYMembraneCurrentsandConductancesTheInsandOutsofActionPotentialTHEACTIONPOTENTIALINREALITYTheVoltage GatedSodiumChannelVoltage GatedPotassiumChannelsPuttingthePiecesTogetherACTIONPOTENTIALCONDUCTIONFactorinfluencingconductionvelocityACTIONPOTENTIALS AXONS ANDDENDRITESCONCLUDINGREMARKS Figure4 11Actionpotentialconduction Figure4 11Actionpotentialconduction Theentryofpositivechargeduringtheactionpotentialcausesthemembranejustaheadtodepolarizetothreshold 已经兴奋的膜部分通过局部电流 刺激 了未兴奋的膜部分 使之出现动作电位 AnactionpotentialpropagatesinonedirectionAnactionpotentialcanbegeneratedbydepolarizationateitherendoftheaxonandthereforepropagateineitherdirection FactorsInfluencingConductionVelocity Actionpotentialconductionvelocityincreaseswithincreasingaxonaldiameter 轴突的直径 Axonalsizeandthenumberofvoltage gatedchannelsinthemembranealsoaffectaxonalexcitability 轴突上钠离子通道的密度 Temperature 温度 MyelinandSaltatoryConduction Myelin 髓鞘 SchwanncellsintheperipheralnervoussystemOligodendrogliainthecentralnervoussystemVoltage gatedsodiumchannelsareconcentratedinthemembraneofthenodesofRanvier 郎飞结 Inmyelinatedaxones actionpotentialsskipfromnodetonode Saltatoryconduction跳跃式传导 MyelinandSaltatoryConduction Inmyelinatedaxones actionpotentialsskipfromnodetonode Saltatoryconduction 75 Chapter4TheActionPotential PROPERTIESOFTHEACTIONPOTENTIALTheUpsandDownsofanActionPotentialsGenerationofanActionPotentialTheGenerationofMultipleActionPotentialsTHEACTIONPOTENTIALINTHEORYMembraneCurrentsandConductancesTheInsandOutsofActionPotentialTHEACTIONPOTENTIALINREALITYTheVoltage GatedSodiumChannelVoltage GatedPotassiumChannelsPuttingthePiecesTogetherACTIONPOTENTIALCONDUCTIONFactorinfluencingconductionvelocityACTIONPOTENTIALS AXONS ANDDENDRITESCONCLUDINGREMARKS Spike initiationzone Onlymembranethatcontainsvoltage gatedsodiumchannelsiscapableofgeneratingactionpotential Voltage gatedsodiumchannelsTheaxons ThedendritesTheaxons ThecellbodiesThepartoftheneuronwhereanaxonoriginatesfromthesoma theaxonhillock 轴丘 isoftenalsocalledthespike initiationzone 动作电位起始点 Figure4 14Membraneproteinspecifythefunctionofdifferentpartsoftheneuron Acorticalpyramidalneuron Aprimarysensoryneuron Chapter4TheActionPotential PROPERTIESOFTHEACTIONPOTENTIALTheUpsandDownsofanActionPotentialsGenerationofanActionPotentialTheGenerationofMultipleActionPotentialsTHEACTIONPOTENTIALINTHEORYMembraneCurrentsandConductancesTheInsandOutsofActionPotentialTHEACTIONPOTENTIALINREALITYTheVoltage GatedSodiumChannelVoltage GatedPotassiumChannelsPuttingthePiecesTogetherACTIONPOTENTIALCONDUCTIONFactorinfluencingconductionvelocityACTIONPOTENTIALS AXONS ANDDENDRITESCONCLUDINGREMARKS NeuronalElectricActivitiesInclude RestPotential Chapter3 ActionPotential Chapter4 LocalPotentialsPost SynapticPotentialExcitatoryPost SynapticPotentialInhibitoryPost SynapticPotentialEnd platePotentialReceptorPotential 80 KEYTERMSANDREVIEWQUESTIONS P72andP97 Thanks