生理学教学课件：04-Circulation2（中英班）

CirculationTwomajortypesofcardiacmuscle:

Workingcell（Atrialmuscle,ventricularmuscle）：contractinthesamewayasskeletalmuscleAutorhythmiccell(Specializedexcitatoryandconductivemuscle):-contractfeebly-automaticrhythmicalelectricaldischargeintheformofactionpotentials(AP)-ConductionofAPthroughtheheart

SpreadofcardiacexcitationSAnodeAtrium

AVnodeBundleofHisRightandleftbundlebranchPurkinjefibersVentricle。ConductingsystemoftheheartGeneralprocessofexcitationandcontractionofcardiacmuscleInitiationofAPinsinoatrialnodeConductionofAPalongspecializedconductivesystemExcitation-contractioncouplingMusclecontraction（Atrialmuscle,ventricularmuscle）Thedifferencesbetweenskeletalmuscleandcardiacmuscle?skeletalmusclecardiacmuscleDifference1：skeletalmusclecardiacmuscleCompletetetanusTetanusisimpossible1.Summation&tetanus(强直收缩）

ofcardiacmuscleisimpossible,why?SummationofContraction-Incompletetetanus-Completetetanus复习电生理知识Na、K、Ca在膜内外的不均衡分布带电离子的跨膜流动引起跨膜电位的变化：极化、去极化、复极化、超极化、反极化APsodium-potassiumpumpCa2+10外正内负——极化状态（polarization）静息电位(restingpotential,RP)极化（

polarization）：静息电位外正内负的状态去极化（depolarization）：静息电位减小反极化（contrapolarization)：膜电位由0电位变为正值复极化（repolarization）超极化（hyperpolarization）：静息电位增大11Na+orCa2+influx—DepolarizationＫ+efflux—RepolarizationTransmembranepotentialofventricularcellsRestingPotential:-90mVActionPotentialPhase0:DepolarizationPhase1:EarlyphaseofrapidrepolarizationPhase2:PlateauPhase3:LatephaseofrapidrepolarizationPhase4:RestingphaseTherefractoryperiodofventriclemuscleismuchlongerthanthatfortheskeletalmuscle(200~300msfortheventriclescomparedwith2~4msfortheskeletalmuscle).skeletalmuscleventriclemusclePeriodicchangesinexcitabilityAbsoluterefractoryperiod（ARP)

:duringphases0~2andabouthalfofphase3,cardiacmusclecannotbeexcitedagain.0123SignificanceThelongrefractoryperiodmeansthatcardiacmusclecannotberestimulateduntilcontractionisalmostoverThismakessummation&tetanusofcardiacmuscleimpossibleThenormalrefractoryperiodoftheventricleislonger,whichisduetothedurationoftheprolongedplateauofactionpotential.

WhatCausestheLongActionPotentialandthePlateau?

ActionpotentialPhase0:rapiddepolarizationandtheovershootThresholdpotential(-70mV)Openingofvoltage-gatedNa+channels

→rapidinfluxofNa+

Ionicmechanismsvoltage-gatedNa+channels

(fastNa+channel)openforonlyafewmsandthenabruptlyclose.Fastresponsecell(快反应细胞）TheextentandvelocityofdepolarizationarelargeFastconductionFastNa+channelmediate0perioddepolarizationPhase1Earlyphaseofrapidrepolarization

K+efflux activatedat–20mV openingfor5~10ms1Phase2：theprolongedplateaulastsforabout150ms. Inwardcurrent Outwardcurrent

(Ca2+) (K+) L-Ca2+channels(slowCa2+

channels）Significanceof“Phase2plateau”ThemajorcharacteristicofventricularmuscleAPdifferentfromskeletalmuscleCausethelongerrefractoryperiodofventricularmuscleL-Ca2+channelsopencontributetocontractionofventricularmuscleThetargetofmanyfactorssuchasneurotransmitters,chemicalfactors,anddrug.Phase3：Latephaseofrapidrepolarization

InactivationofCa2+channel OutwardK+currentdominates

3Phase4restingstage电位稳定于静息电位水平-与自律细胞区别机制:恢复膜内外离子浓度梯度：-Na+-K+泵-Na+-Ca2+交换（3：1）-Ca2+泵 Actionpotentialduration(APD):200~300ms APD“self-excitation”Difference2voluntarymuscleSinoatrialnode（窦房结）

normalcardiacpacemakerInthesuperiorlateralwalloftherightatriumneartheopeningofthesuperiorvenacavaSpontaneousdischarge(self-excitation)Autorhythmicity(自律性）Itsrateofdischargedeterminingtherateoftheheartbeats.Autorhythmicity自律性SAnode 100times/minAVnode 50times/minBundleofHis 40times/minPurkinjefibers 25times/min2.WhyistheSAnodeabletotriggertheAPautomatically?Maximalrepolarizationpotential-70mVThresholdpotential-40mVPhase0,3,4SinoatrialPcells:autorhythmiccells

403IonicmechanismThepacemakerpotentialThemembranepotentialgraduallyrises.(spontaneousdepolarization)Whenthepotentialreachesathresholdvoltageofabout-40mv,triggersthenextAPspontaneousdepolarizationActionpotentialThresholdpotentialPhase4：-spontaneousdepolarizationIkdecay-K+efflux↓Inactivatedwhenrepolarizedto-60mVIf↑-Na+influx↑ICa,T-Ca2+influx↑

T-typeCa2+channelactivatedwhendepolarizedto-50mVPhase0:Depolarization

Ca2+

influx

(ICa,L)

activationofL-typeCa2+

channel(slowcalciumchannel)403Phase3:Repolarization

InactivationofL-typeCa2+channelOutwardK+current(Ik)403TypesofCa2+channelsincardiaccells:

L-type(long-lasting)(2)T-type(transient)Ca2+channelsDurationofcurrent

long-lasting

transientActivation slower faster Inactivation slower fasterThreshold

high(-40mV) Low(-50mV)Function

producetheAPcomplete4phase

L-type T-type2.Theatriacontractabout0.1saheadofventricularcontraction,why?SAnode Atria A-Vnode

0.05m/s 0.4m/s 0.02~0.05m/sHisbundle Purkinjefiber Ventricle1.2~2.0m/s 2.0~4.0m/s

1.0m/s

ConductingvelocityAVnodaldelay(Atrioventriculardelay)

房室延搁Theatrialmuscleareseparatedfromthoseofventriclesbyafibroustissuering.TheAVnodeisnormallytheonlyconductingpathwaybetweentheatrialandventricles.BecauseconductionintheAVnodeisslow,adelayofabout0.1soccoursbeforeexcitationspreadtotheventricles.CauseoftheSlowConductionintheAVnodediminishednumbersofgapjunctionsbetweensuccessivecellsSmallinsizeAVnode：

slowresponseautorhythmiccell(慢反应自律细胞）:0：L-typeCa2+

channel(slowcalciumchannel)Slowresponsecell(慢反应细胞）TheextentandvelocityofdepolarizationaresmallSlowconductionSlowCa2+channelmediate0perioddepolarizationSignificanceofAVnodaldelay:Theatriacontractabout0.1saheadofventricularcontractionThisdelayallowstimefortheatriatoemptytheirbloodintotheventriclesbeforeventricularcontractionbegins.Difference3：skeletalmusclecardiacmuscleSizeprinciple(八版P50)contractsimultaneouslyCardiacMuscleasaSyncytium(合胞体)

Thecardiaccellsaresointerconnectedthatwhenoneofthesecellsbecomesexcited,theAPspreadstoallofthem.

Allportionsoftheventriclescontractalmostsimultaneously4.WhyareAPabletotraveleasilyfromonecardiacmusclecelltothenext?Cause1：Gapjunctions(缝隙连接）:

allowfreediffusionofions

APtraveleasilyfromonecardiacmusclecelltothenext,pasttheintercalateddiscs（闰盘）.

Gapjunctions

intercalateddiscsAdjacentcellmembranesCause2:PurkinjeSystemRapidtransmissionofactionpotentials：

Atavelocityof2~4m/sIonmechanism：

Largehighlevelofthegapjunctionsfastresponseautorhythmiccell

（快反应自律细胞）0：Na+(fastNa+channel)4：If↑

IK↓1,2,3:similartoventricularmuscle012433RoleofthePurkinjeSysteminCausingSynchronousContractionoftheVentricularMuscleItisfromthepurkinjesystemthatthecardiacimpulsearrivesatalmostallportionsoftheventricleswithinanarrowspanoftimeAllportionsoftheventricularmusclebegincontractingatalmostthesametimeEffectivepumpingbytheventriclesrequiresthissynchronous（同步的）typeofcontraction√心室肌细胞AP的离子机制总结0期Na+内流(快Na+通道)1期K+外流(Ito通道)2期Ca2+内流(慢Ca2+通道)K+外流(IK,IK1通道)3期K+外流(IK,IK1通道)4期Na+-K+泵

Na+-Ca2+交换

Ca2+泵HomeworkDscribetheionmechanismofactionpotentialinventricularmuscleDscribethesignificanceof“plateau”ComparetheactionpotentialsinventricularmusclewiththoseinskeletalmuscleComparetheactionpotentialsinventricularmusclewiththoseinautorhythmiccellListandexplaintheeffectsofslowcalciumchannelblockingdrugsontheheart.Inwhichclinicalconditionsaretheyofvalue?GeneralquestionIntensivereadingTextbookofMedicalPhysiology(Guyton&Hall)104120ExcitabilityConductivityAutorhythmicityContractilityElectrophysiologicalpropertiesMechanicalpropertyPhysiologicalpropertiesofcardiaccellsWorkingcell：Excitability、Conductivity、ContractilityAutorhythmiccell：Autorhythmicity

、Excitability、ConductivityAbilityofgeneratingAPafterstimulationbereverselyproportionaltothreshold(阈值）Ⅰ.Excitability兴奋性1.PeriodicchangesinexcitabilityAbsoluterefractoryperiod(ARP)LocalresponseperiodEffectiverefractoryperiod(ERP)Relativerefractoryperiod(RRP)Supranormalperiod(SNP)Effectiverefractoryperiod(ARP)（p69）:

TheperiodduringwhichasecondAPcannotbeelicited,evenwithastrongstimulus.RestingpotentialThresholdpotentialStatusofNa+orCa2+channels2.FactorsaffectingexcitabilityVoltage-gatedNa+channels

(fastNa+channel)DepolarizationRepolarizationReopen:themembranepotentialreturntoorneartherestingpotentiallevelExplanationThelongrefractoryperiodmeansthatcardiacmusclecannotberestimulateduntilcontractionisalmostoverSummation&tetanusofcardiacmuscleisimpossibleSystole

and

diastole

occurs

alternately

which

is

very

important

for

the

heart

to

pump

blood

into

arteries3.EffectofperiodicchangesinexcitabilityonmyocardiumcontractionPrematuresystole&compensatorypause

Premature

systole

is

generally

followed

by

a

so-called

conmpensatory

pause,

because

the

heart

is

still

in

the

absolute

refractory

period

of

the

extrasystole

when

the

excitatory

impulse

from

the

sa

node

arrives.Compensatorypause代偿间隙:Premature

systole

is

generally

followed

by

a

so-called

conmpensatory

pause,

because

the

heart

is

still

in

the

absolute

refractory

period

of

the

extrasystole

when

the

excitatory

impulse

from

the

SA

node

arrives.Premature

systole.

This

is

a

contraction

of

the

heart

prior

to

the

time

that

normal

contraction

would

have

been

expected.Prematuresystole期前收缩extrasystole:a

contraction

of

the

heart

prior

to

the

time

that

normal

contraction

would

have

been

expectedⅡ.ConductivitySAnodeAtrium

AVnodeBundleofHisRightandleftbundlebranchPurkinjefibersVentricle。ConductingsystemoftheheartⅡ.Conductivity传导性Gapjunctions(缝隙连接）:allowAPtraveleasilyfromonecardiacmusclecelltothenext,pasttheintercalateddiscs（闰盘）.

intercalateddiscsAdjacentcellmembranesGapjunctionsmediaterapidtransmissionofAPbetweenadjacentcardiacmusclecellSAnode Atria A-Vnode

0.05m/s 0.4m/s 0.02~0.05m/sHisbundle Purkinjefiber Ventricle1.2~2.0m/s 2.0~4.0m/s

1.0m/s

ConductingvelocityAtrioventriculardelay

房室延搁TheAVnodeisnormallytheonlyconductingpathwaybetweentheatrialandventricles.BecauseconductionintheAVnodeistheslowest,adelayofabout0.1soccoursbeforeexcitationspreadtotheventricles.Theatriacontractabout0.1saheadofventricularcontractionThisdelayallowstimefortheatriatoemptytheirbloodintotheventriclesbeforeventricularcontractionbeginsRapidtransmissionofAPinthePurkinjeSystemCausingSynchronousContractionoftheVentricularMuscleItisfromthepurkinjesystemthatthecardiacimpulsearrivesatalmostallportionsoftheventricleswithinanarrowspanoftimeAllportionsoftheventricularmusclebegincontractingatalmostthesametimeEffectivepumpingbytheventricularrequiresthissynchronoustypeofcontractionFactorsAffectingConductivityStructuralfactorsDiameterofcardiaccellsGapjunctionsatIntercalateddiskPhysiologicalfactorsThevelocityandamplitudeofphase0depolarizationExcitabilityofadjacentregion0期除极速度快局部电流形成快临近未兴奋膜达到阈电位快兴奋传导快0期除极幅度大(兴奋和未兴奋部位之间)电位差大局部电流强，扩布距离大，使下游更远处兴奋兴奋传导快1）动作电位0期去极化速度和幅度静息电位与阈电位的差距扩大兴奋性降低达阈电位所需时间长传导减慢兴奋不能引起兴奋传导阻滞传导减慢2）邻近部位膜的兴奋性升支缓慢、幅度小的动作电位相对不应期或超常期内有效不应期PurkinjefiberAVnodevelocityFastest（4m/s）Slowest（0.02m/s）DiameterofcellsBig(70um)Small(0.3um)GapjunctionmanyfewThevelocityandamplitudeofphase0depolarizationFastresponsecellslowresponsecellsignificanceSynchronousContractionoftheVentricularMuscleAtriumcontrataheadofventricularcontracitonⅢ.Autorhythmicity自律性

AbilitytotriggertheAPautomaticallyAutorhythmicitySAnode 100times/minAVnode 50times/minBundleofHis 40times/minPurkinjefibers 25times/minNormalpacemakerSAnodeLatentpacemaker(Ectopicpacemaker异位起搏点under pathophysiologicalconditions) AVnode BundleofHis PurkinjefibersThemechanismsofSAnodetocontrollatentpacemakersCapture抢先占领Overdrivesuppression超速驱动压抑FactorsAffectingAutorhythmicityThevelocity（slope）ofphase4spontaneousdepolarizationMaximalrepolarizationpotentialThresholdpotentialPacemaker1.SynchronousContraction：Theheartiscomposedoftwosyncytiums(合胞体）:theatrialsyncytiumandtheventricularsyncytium.2.Tetanusisimpossible：longERP3.[Ca2+]0-dependent：兴奋-收缩脱偶联：当胞外钙浓度很低甚至无钙时，心肌细胞虽仍能产生动作电位，却不能引起收缩。Ⅳ.Contractivity钙触发式钙释放(calcium-inducedcalciumrelease)请问:Kcl能静脉注射吗?为什么?

Effectofpotassiumonheartfunction(p112)正常血钾是3.5-5.5mmol/L轻度高K+（5~7mmol/L）时，由于静息电位略有减小，与阈电位水平之间差距减小，兴奋性增高。当细胞外K+显著增高（8~12mmol/L），则因静息电位显著降低（-55至-60mV）-而引起Na+通道处于失活状态，干扰0期去极化，兴奋性、传导性反而降低；-膜对K+通透性增加，4期K+外流衰减减慢，干扰4期自动去极化，自律性降低-K+外流增加，平台期缩短，干扰2期钙内流，收缩性下降。

-心脏收缩减弱、心律失常、心脏停搏Electrocardiogram(ECG)心电图Theelectrocardiographisadevicetorecordtheelectricalsignalsproducedbytheheartbyplacingelectrodesonthesurfaceoftheskin.Therecordingobtainediscalledtheelectrocardiogram(ECG).TheECG