membrane potentials and synapses - mt. sac...membrane potentials and synapses physiology unit 2. in...

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