membrane potentials and synapses - mt. sac...membrane potentials and synapses physiology unit 2. in...
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MEMBRANEPOTENTIALSandSYNAPSES
PhysiologyUnit2
InPhysiologyTodayApril1,2020
• Membranepotentials• Synapses• InLabNextTime– That’scute– Wecan’thavereallabs– I’llgooverlabstufflater
InformationFlow
NeuronCommunication
• Neuronsarestimulatedbyreceptorsondendritesandcellbodies(soma)– Ligandgatedionchannels– GPCR’s
• NeuronsstimulatecellsbyreleasingNTfromsynapticbulbs– Bindstoreceptorsonthe
effectorcell– Ligandgatedionchannels– GPCR’s
NeuronCommunication
• NeuronsstimulatecellsbyreleasingNT– Thestimuluswilltriggeracellularresponseintheeffectorcell
• NTisreleasedfromthesynapticbulb• NTreleaseistheresultofanelectricalcurrenttravelingdowntheaxonreachingthesynapticbulb
• Acurrent istheflow/movementofanelectricalcharge
• Anelectricalcurrent canonlybegeneratedincellswithexcitablemembranes
Current
Ohm’sLawI=V/R• Thecurrent(I) throughaconductorisdirectlyproportionaltothevoltage(V) acrossthetwopointsandinverselyproportionaltotheresistance(R)betweenthem.
• Theplasmamembraneistheconductor• Voltage(V)=ElectricalpotentialmeasuredinmV• Current(I)=Movementofelectricalcharge• Resistance(R)=Factorsthatpreventmovement
– Plasmamembranes(lipids)havehighelectricalresistance– Waterhaslowelectricalresistance(cytoplasm,ECF)
ExcitableMembranes
Membranescapableofgeneratingavoltage
NeuronsMusclecells
Afewothers(endocrine,immune,reproductive)
• Voltage =differenceinthechargeacrossamembrane
• Ionsarecharged• Cellmembranesseparate
ionsacrossthemembrane– Membranesare
semipermeable– Membranesarepermeableto
ionsthroughionchannels– Cellsmaintainconcentration
gradientsofions
ReceptorsInvolvedinDetectingaStimulus
MembranePotential
• Membranepotential(mV)isthedifferenceinchargeacrossthemembrane
• Extracellularfluid(IF)voltageissetat0
• MembranepotentialisreportedcomparedtothevoltageoftheIF– Inside<Outside(-)value– Inside>Outside(+)value
MembranePotential
• Ionsthatcanmoveacrossthemembranecollectinathinshellveryclosetoeachsideofthemembrane
• Thebulkoftheintracellularandextracellularionsinthefluidsremainthesame
EquilibriumPotential
• Theoretical voltageproducedacrossacellmembranewiththemovementofonlyONEion
• Individualionshavedifferentmembranepermeabilities– Ionchannelspresent– Characteristicsofionchannels(gated,leaky)
• Eachioncontributesitsownvoltagetotheoverallmembranepotentialofamembrane
EquilibriumPotential
• TheNernstEquationcalculatestheequilibriumpotentialofasingleion
– Eion =equilibriumpotentialofaparticularioninmV– Ci =concentrationofioninsidethecell– Co =concentrationofionoutsidethecell– Z=valenceofion
Eion =_61_log(Co/Ci)Z
EquilibriumPotential
ElectrochemicalgradientsfavorInwardmovementofNa+OutwardmovementofK+
EquilibriumPotential
Equilibriumpotentialofeachioncontributestotheoverallmembranepotential
ofacell
ENa+ +61mV
EK+ -90mV
RestingMembranePotential(RMP)
• RestingMembranePotential(RMP)isthedifferenceinchargeacrossthemembraneinarestingcell– TheoveralldifferencechargefromALL oftheionsthatmoveacrossthemembrane
Arestingcellisnotreceivingastimulus
RestingMembranePotential(RMP)
RMP isestablishedandmaintainedby:
Na+/K+/ATPasepump
Thepermeabilityofthemembranetoions
RestingMembranePotential(RMP)Na+/K+/ATPasePump
• Alwayspumping3(+)chargesoutand2(+)chargesin
• Generatesa(-)potential
RestingMembranePotential(RMP)ThePermeabilityoftheMembranetoIons
• RMPofneuronsrangefrom-20mVto-90mV– Membraneispolarized
• AverageRMPis-70mV
• Permeabilityismovementacrossthemembrane• Ionsmovethroughion
channels– Ionsthatmoveacrossall
excitablemembranesareNa+ andK+
– K+ hasagreaterpermeabilitythanNa+
Arestingcellisnotreceivingastimulus
Voltage-GatedIonChannelsFoundontheAxonandSynapticBulb
Navg+ channels• Allaregated• ClosedatRMP• Fasttoopen• Fasttoinactivate– Haveinactivationgates• Intracellularstructure• Stopsionfluxbyblockingionchannels
Kvg+ channels• Mostaregated– ClosedatRMP– Slowtoopen– Slowtoclose
• SomeareLeaky– “leak”atthreshold– Allowaslow,steadyfluxofK+ atthreshold
– Generatesa(-)potential
Voltage-GatedNa+ andK+ Channels
ChangesinMembranePotential
Membranesarepolarizedatrest:–70mV• Depolarizingamembrane
– Astimuluscausesthevoltagetochangeandmovetowards0mv– Causedbytheinwardmovementofa(+)ion:Na+,Ca2+
• Repolarizingamembrane– Thevoltagechangesandmovestowardstheresting,polarizedvoltage– Causedbytheoutwardmovementofa(+)ion:K+
• Hyperpolarizingamembrane– Thevoltagechangesandbecomesmorepolarized(voltage<-70mV)– Causedbytheinwardmovementofa(-)ion:Cl-
– Causedbytheoutwardmovementofa(+)ion:K+
ChangesinMembranePotential
• Depolarization– Causedbytheinward
movementofa(+)ion:Na+,Ca+
• Repolarization– Causedbytheoutward
movementofa(+)ion:K+
• Hyperpolarization– Causedbytheinward
movementofa(-)ion:Cl-
– Causedbytheoutwardmovementofa(+)ion:K+
Membranepotentialmaychange100mV
ChangesinMembranePotential
• Gradedpotentials– Transmitinfooverashortdistance– Dendrites,soma,NMJ–Movesthemembranetowardsthresholdorawayfromthreshold
• Actionpotentials– Transmitinfooveralongdistance– Axonsandmusclecellmembranes– ResultsinthereleaseofNT
DifferenceBetweenGradedPotentialsandActionPotentials
GradedPotentials
• Transientchangesinmembranepotential– DuetothemovementofNa+,
K+,Ca2+,Cl-
• Occurwhereastimulusisreceived
• Variablemagnitude– Changesthemembrane
potentialtowardsthreshold– Changesthemembrane
potentialawayfromthreshold
• “FizzleOut”– Conducteddecrementally
GradedPotentials
• 4TypesofGradedPotentials• Sensorypotential– Occursonsensoryreceptors
• Synapticpotential– Occursatanervetonervesynapse
• Pacemakerpotential– Occursonpacemakercellsoftheheart(SANode)
• EPP– Occursonthemotorendplateofskeletalmuscle
ActionPotentials
• Rapidreversalofmembranepotential– DuetothemovementofNa+ andK+
• Triggeredbythemembranereachingthreshold– Gradedpotentialsmoveamembranetowardsthreshold
• Resultsinthereleaseofaneurotransmitter• OneWayconduction– Travelsinonedirectiondowntheaxontothesynapticbulb
• Propagatedacrossaxons,musclecellmembranes• Allornothingresponse• Actionpotentialsarerapid(0.5-100m/s)
StepsofAP1. RMP2. Threshold3. Membranedepolarizes4. Membranestops
depolarizing5. Membranerepolarizes6. Membrane
hyperpolarizes7. RMP
StepsofAP1. RMP2. Threshold3. Membranedepolarizes4. Membranestops
depolarizing5. Membranerepolarizes6. Membrane
hyperpolarizes7. RMP
ActionPotentialMechanism
1. RMP maintainedduetoNa+/K+/ATPasepumpsandleaky K+channels
2. Astimuluscausesthemembranevoltagetoreachthreshold3. voltage-gated Na+ channelsopencausingthemembraneto
quicklydepolarize4. voltage-gatedNa+ channelsarequicklyinactivated.
Membranedepolarizationstops.4. voltage-gated K+ channelsopenandthemembranebegins
torepolarize6. voltage-gated K+ channelsclose7. Na+/K+/ATPasepumpsreestablishRMP
OneWayConduction
• APonlytravelsdowntheaxontothesynapticbulb
• Presynapticmembranetopostsynapticmembrane
OneWayConduction
• RefractoryperiodsensuretheAPmovesinonedirectiondowntheaxon– Aperiodimmediatelyfollowingstimulationduringwhichanerveormuscleisunresponsiveorlessresponsivetofurtherstimulation
• PreventsasubsequentAPfrombeginningbeforethefirstAPiscomplete
• LimitsnumberofAPanervecanproduceinagiventimeperiod
AbsoluteRefractoryPeriod
• FollowstheAP• CannotproduceanAPonthemembrane
• Na+ channelsinactivated
• Na+ channelscannotopen
• Nowaytodepolarizethemembrane
RelativeRefractoryPeriod
• Followstheabsoluterefractoryperiod
• CanproduceanAPonthemembrane
• Na+ channelsarenowclosed
• Axonmembraneishyperpolarized
• Strongerthannormalstimulusrequired
RefractoryPeriods
• Absoluterefractoryperiod– Na+ channelsinactivated
• Relativerefractoryperiod– Na+ channelsarenowclosed
ActionPotentialPropagation
• AnAPcanonlytravelthelengthofanaxonifeachpointalongthemembraneisdepolarizedtothreshold
• ThecurrentduringanAPissufficienttoeasilydepolarizetheadjacentmembranetothresholdpotential– Ionsleaktonextsegment,initiatingAP– Sequentialopening/closingofNa+ andK+ channelsalongthemembrane
• APdoesnotmove,itsetsoffanewAPintheregionjustaheadofit
ActionPotentialPropagation(APtravelsdownaxon)
ActionPotentialVelocity
• VelocityofAPisdeterminedby:
• Diameteroffiber– Small– slower– Large- faster
• Myelination– Insulation– Increasesspeedofconduction
– NodesofRanvier– Saltatory conduction
ConductionVelocitiesSmall,unmyelinated– 0.5m/sLarge,myelinated– 100m/s
ActionsPotentialVelocity
• Unmyelinated axons– Depolarizationofeachsegment
– Slower
• Myelinated axons– Saltatoryconduction– NodesofRanvier– Na+ channelconcentration– Faster
ActionPotentialsareAll-or-None
• Membraneapproachingthreshold– SubthresholdstimulidonotgenerateanAP
• Membranereachesthreshold– Ifthresholdisreached,depolarizationproceedswiththesameamplitude
ReleaseofNeurotransmitter
• NTisreleasedfromthesynapticbulb– Functionalconnectionbetweencells
• NTisachemical• Chemicalsynapse– Synapticbulb– Synapticcleft– Synapticvesicles– Neurotransmitter
ChemicalSynapse
ChemicalSynapse• Presynapticmembraneis
separatedfromthepostsynapticmembranebysynapticcleft
• NTreleasedfromsynapticvesicles
• VesiclesfusewithaxonmembraneandNTreleasedbyexocytosis
• AmountofNTreleaseddependsuponfrequencyofAP
* N-type Ca2+ Channels present in the synaptic bulb
VideostoWatch
• Don’tforgettowatchthevideos Ipostedlinkstoincanvasto helpunderstandNTrelease.
• Youareonlyresponsibleforthedetailinthislecture.Oneofthevideosgoesintoalotmoredetailofvesicledocking.
1. 2-MinuteNeuroscience:NeurotransmitterRelease
2. NeurotransmitterRelease
3. ReleaseofNeurotransmitter