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1、LIUChuanYong刘传勇InstituteofPhysiologyMedicalSchoolofSDUTel88381175(lab)88382098(office)Email:Website:1 1Section2BioelectricalPhenomenaoftheCell2 2Basic ConceptsVoltA charge difference between two points in space3 3Basic ConceptsIonschargedparticlesAnionsNegativelychargedparticlesCationsPositivelychar
2、gedparticles4 4Basic ConceptsForces that determine ionic movementElectrostaticforcesOppositechargesattractIdenticalchargesrepelConcentrationforcesDiffusionmovementofionsthroughsemipermeablemembraneOsmosismovementofwaterfromregionofhighconcentrationtolow5 5Selective Permeability of MembranesSomeionsp
3、ermittedtocrossmoreeasilythanothersNeuronalmembranescontainionchannelsProteintubesthatspanthemembraneSomestayopenallthetime(nongated)Someopenontheoccasionofanactionpotential,causingachangeinthepermeabilityofthemembrane(gated)6 6I.Membrane Resting PotentialAconstantpotentialdifferenceacrosstheresting
4、cellmembraneCellsabilitytofireanactionpotentialisduetothecellsabilitytomaintainthecellularrestingpotentialatapproximately70mV(-.07volt)Thebasicsignalingpropertiesofneuronsaredeterminedbychangesintherestingpotential7 7Membrane Resting PotentialEveryneuronhasaseparationofelectricalchargeacrossitscellm
5、embrane.Themembranepotentialresultsfromaseparationofpositiveandnegativechargesacrossthecellmembrane.8 8Membrane Resting Potentialexcessofpositivechargesoutsideandnegativechargesinsidethemembranemaintainedbecausethelipidbilayeractsasabarriertothediffusionofions givesrisetoanelectricalpotentialdiffere
6、nce,whichrangesfromabout60to70mV.(Microelectrode)9 9Concept of Resting Potential(RP)Apotentialdifferenceacrossthecellmembraneatthereststageorwhenthecellisnotstimulated.Property:ItisconstantorstableItisnegativeinsiderelativetotheoutsideRestingpotentialsaredifferentindifferentcells.1010Ion ChannelsTwo
7、TypesofIonChannelsGatedNon-Gated1111Resting Membrane PotentialNa+andCl-aremoreconcentratedoutsidethecellK+andorganicanions(organicacidsandproteins)aremoreconcentratedinside.1212Intracellular vs extracellular ion concentrationsIon Intracellular ExtracellularNa+5-15 mM 145 mMK+140 mM 5 mMMg2+0.5 mM 1-
8、2 mMCa2+10-7 mM 1-2 mMH+10-7.2 M(pH 7.2)10-7.4 M(pH 7.4)Cl-5-15 mM 110 mM1313Resting Membrane PotentialPotassiumions,concentratedinsidethecelltendtomoveoutwarddowntheirconcentrationgradientthroughnongatedpotassiumchannelsButtherelativeexcessofnegativechargeinsidethemembranetendtopushpotassiumionsout
9、ofthecell1414Potassium equilibrium-90mV1515Resting Membrane PotentialBut what about sodium?ElectrostaticandChemicalforcesacttogetheronNa+ionstodrivethemintothecellTheNa+channelcloseduringtherestingstateNa+ismoreconcentratedoutsidethaninsideandthereforetendstoflowintothecelldownitsconcentrationgradie
10、ntNa+isdrivenintothecellbytheelectricalpotentialdifferenceacrossthemembrane.1616Na+electrochemical gradient1717Equilibrium PotentialsTheoreticalvoltageproducedacrossthemembraneifonly1ioncoulddiffusethroughthemembrane.IfmembraneonlypermeabletoK+,K+diffusesuntilK+isatequilibrium.Forceofelectricalattra
11、ctionanddiffusionare=opposite.1818Calculating equilibrium potentialNernst EquationAllowstheoreticalmembranepotentialtobecalculatedforparticularion.Membranepotentialthatwouldexactlybalancethediffusiongradientandpreventthenetmovementofaparticularion.Valuedependsontheratioofiononthe2sidesofthemembrane.
12、1919Nernst equationEquilibrium potential(mV),Eion=lnRTzFCoCiwhere,Co and Ci=extra and intracellular ion R=Universal gas constant(8.3 joules.K-1.mol-1)T=Absolute temperature(K)F=Faraday constant(96,500 coulombs.mol-1)z=Charge of ion(Na+=+1,Ca2+=+2,Cl-=-1)For K+,with K+o=4 mmol.l-1 and K+i=150 mmol.l-
13、1At 37C,EK=-97mV ENa=+60mv2020K+o=4 mmol.l-12121Resting Membrane PotentialRestingmembranepotentialislessthanEkbecausesomeNa+canalsoenterthecell.TheslowrateofNa+influxisaccompaniedbyslowrateofK+outflux.Dependsupon2factors:Ratiooftheconcentrationsofeachiononthe2sidesoftheplasmamembrane.Specificpermeab
14、ilityofmembranetoeachdifferention.Restingmembranepotentialofmostcellsrangesfrom-65to85mV.2222The Sodium-Potassium PumpDissipation of ionic gradients is ultimately prevented by Na+-K+pumpsextrudes Na+from the cell while taking in K 2323Resting Potential2424The formation of resting potential depends o
15、n:ConcentrationdifferenceofK+acrossthemembranePermeabilityofNa+andK+duringtherestingstateNa+-K+pump2525FactorsthataffectrestingpotentialDifferenceofK+ionconcentrationacrossthemembranePermeabilityofthemembranetoNa+andK+.ActionofNa+pump2626Basic Electrophysiological Terms I:Polarization:astateinwhichm
16、embraneispolarizedatrest,negativeinsideandpositiveoutside.Depolarization:themembranepotentialbecomeslessnegativethantherestingpotential(closetozero).Hyperpolarization:themembranepotentialismorenegativethantherestinglevel.2727Basic Electrophysiological Terms I:Reverspolarization:a reversal of membran
17、e potential polarity.The inside of a cell becomes positive relative to the outside.Repolarization:restoration of normal polarization state of membrane.a process in which the membrane potential returns toward from depolarized level to the normal resting membrane value.2828II Action PotentialSuccessiv
18、eStages:(1)RestingStage(2)Depolarizationstage(3)Repolarizationstage(4)After-potentialstage(1)(2)(3)(4)2929ConceptActionpotentialisarapid,reversible,andconductivechangeofthemembranepotentialafterthecellisstimulated.Nervesignalsaretransmittedbyactionpotentials.3030Action Potential SequenceVoltage-gate
19、d Na+Channels open and Na+rushes into the cell3131Action Potential SequenceAt about+30 mV,Sodium channels close,but now,voltage-gated potassium channels open,causing an outflow of potassium,down its electrochemical gradient3232Action Potential Sequenceequilibrium potential of the cell is restored333
20、3Action Potential SequenceThe Sodium Potassium Pump is left to clean up the mess3434IonPermeabilityduringtheAPIonPermeabilityduringtheAPFigure8-12:Refractoryperiods3535Basic Electrophysiological Terms II(1)Excitability:The ability of the cell to generate the action potentialExcitable cells:Cells tha
21、t generate action potential during excitation.in excitable cells(muscle,nerve,secretery cells),the action potential is the marker of excitation.Some scholars even suggest that in excitable cells,action potential is identical to the excitation.3636Basic Electrophysiological Terms II(2)Stimulus:a sudd
22、en change of the(internal or external)environmental condition of the cell.includes physical and chemical stimulus.The electrical stimulus is often used for the physiological research.Threshold(intensity):the lowest or minimal intensity of stimulus to elicit an action potential(Three factors of the s
23、timulation:intensity,duration,rate of intensity change)3737Basic Electrophysiological Terms II(3)Types of stimulus:Threshold stimulus:The stimulus with the intensity equal to thresholdSubthreshold stimulus:The stimulus with the intensity weaker than the thresholdSuprathreshold stimulus:The stimulus
24、with the intensity greater than the threshold.3838Action Potential SummaryReductioninmembranepotential(depolarization)tothresholdlevelleadstoopeningofNa+channels,allowingNa+toenterthecellInteriorbecomespositiveTheNa+channelsthencloseautomaticallyfollowedbyaperiodofinactivation.K+channelsopen,K+leave
25、sthecellandtheinterioragainbecomesnegative.Processlastsabout1/1000thofasecond.3939PropertiesoftheActionPotential“Allornone”phenomenonAthresholdorsuprathresholdstimulusappliedtoasinglenervefiberalwaysinitiatethesameactionpotentialwithconstantamplitude,time courseandpropagation velocity.PropagationTra
26、nsmittedinbothdirectioninanervefiber4040IIIInitiationofActionPotential 4141Squid giant axon4242Gated channel states4343CO2HOutsideNH2+InsideNa+Channel a1-Subunit StructureIIIIIIIVRVIRLARIGRILRLIKGAKGIR+IFMIFM-Inactivation“Gate”IVS4 Voltage SensorNH2CO2Hb b1 14444Voltage gatedBut“ready”Not“ready”4545
27、Activation&FastInactivation4646Sodium Activation and Inactivation Variable Sodium Activation and Inactivation Variable vs Voltagevs VoltageActivation GateActivation GateInactivation gateInactivation gateIfrestingpotentialdepolarizedby1520mV,thenactivationgateopenedwith5000 xincreaseinNa+permeability
28、followedbyinactivationgateclose1mslater4747Positive feedback loopReach“threshold”?IfYES,then.Stimulation4848Action potential initiationS.I.Z.4949Action potential termination50505151Threshold PotentialThreshold potentialplaysakeyroleinthegenesisofactionpotential.Threshold potentialisacriticalmembrane
29、potentiallevelatwhichanactionpotentialcanoccur.WhycanalltheNa+channelopenatthethresholdpotential?Itisdependentonthegatingpropertyofthevoltage-gatedNa+channels.Thevalueofthresholdpotentialofmostexcitablecellmembraneisabout15to20mVlessnegativethantherestingpotential.Thethreshold stimulusisjuststrongen
30、oughtodepolarizethemembranetothethresholdpotentiallevel,thereforeitcancauseanactionpotential.5252Electrophysiological Method to Record Membrane Potential IVoltageClamp5353 The Nobel Prize in Physiology or Medicine(1963)“for their discoveries concerning the ionic mechanisms involved in excitation and
31、 inhibition in the peripheral and central portions of the nerve cell membrane”Alan Lloyd HodgkinAndrew Fielding Huxley5454ColeandcolleaguesdevelopedamethodformaintainingVmatanydesiredvoltagelevel(FBA,FeedbackAmplifier)Requiredmonitoringvoltagechanges,feedingitthroughanamplifiertodrivecurrentintoorou
32、tofthecelltodynamicallymaintainthevoltagewhilerecordingthecurrentrequiredtodosoThevoltageclamp5555The Hodgkin-Huxley Model of Action Potential Generation56565757Triphasic response5858Evidence for a Sodium CurrentRemove extracellular sodium5959Modern proof of nature of currentsUse ion selective agent
33、s6060RemovingNa+fromthebathingmedium,INabecomesnegligiblesoIK canbemeasureddirectly.SubtractingthiscurrentfromthetotalcurrentyieldedINa.61616262Conductance of Na+and K+channels6363Voltage-DependenceofConductance6464An action potential gNa increases quickly,but then inactivation kicks in and it decre
34、ases again.gK increases more slowly,and only decreases once the voltage has decreased.The Na+current is autocatalytic.An increase in V increases gNa,which increases the Na+current,and increases V,etc.Hence,the threshold for action potential initiation is where the inward Na+current exactly balances
35、the outward K+current.6565for their discoveries concerning the function of single ion channels in cellsThe Nobel Prize in Physiology or Medicine(1991)Erwin NeherBert Sakmann6666CytoplasmIon channelsGiga-sealGlassmicroelectrodeSuction1 mPatch clamp recordingCellMembrane67676868100 ms4 pAClosedOpenSin
36、gle channel record6969Oneresultfrompatchclampstudieswasthefindingthationchannelsconductcurrentsinanallornothingfashion7070Voltage-dependentChannelConductance7171HowchannelconductancesaccumulateNextpageshowsanidealizedversion72727373Inactivating Na+channel currents 7474IVLocalResponse7575Graded(local
37、)potential changes2xmorechemical=2xmorepotentialchange7676LocalResponseDefinition:Local response is a small change in membrane potential caused by a subthreshold stimulusProperties:It s a graded potentialIts propagation is electronic conductionIt can be summed by two ways Spatial summation Temporal
38、summation7777ExcitatoryExcitatoryInhibitoryTimeMembrane Potential (mV)Spatial Summation Spatial Summationabcdabcd7878ExcitatoryExcitatoryInhibitoryTimeMembrane Potential (mV)Temporal&Spatial SummationTemporal Summationabcdabcd7979Distribution of channelsLeak channels everywhere Axon Hillock(Trigger
39、Zone)8080RoleoftheLocalPotentialFacilitatethecell.ThismeansitincreaseexcitabilityofthestimulatedcellCausethecelltoexciteonceitissummedtoreachthethresholdpotential81818282V.PropagationoftheActionPotential838384848585Myelinated neuron of the central nervous system8686Saltatory conduction:The action po
40、tential jumps from node to node87878888Saltatory Conduction8989SaltatoryConductionThepatternofconductioninthemyelinatednervefiberfromnodetonodeItisofvaluefortworeasons:veryfastconservesenergy.90909191FactorsthataffectthepropagationBioelectricpropertiesofthemembraneVelocityandamplitudeofmembranedepol
41、arization9292V Excitation and Excitability of the Tissue9393ExcitationandExcitabilityoftheTissueReview:ExcitationandExcitableCellReview:ThresholdStimulationandExcitabilityChangeofExcitabilityaftertheExcitation94949595Slide3of2896964.Factors that Determine the ExcitabilityRestingpotentialThresholdpot
42、entialConcentrationofextracellularCa2+9797Ifrestingpotentialdepolarizedby1520mV,thenactivationgateopenedwith5000 xincreaseinNa+permeabilityfollowedbyinactivationgateclose1mslaterActivation GateActivation GateInactivation gateInactivation gate9898the threshold for action potential initiation is where
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