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Cardiac Electrophysiology andElectrocardiogram Interpretation

Cellular Excitation

Theheart is an excitabletissuebecauseitscellseach,individually,generateandcommunicatethiselectrical activity. Eachmyocyteintheheartiscapable ofsupportingitsbasicpatternofelectricalbehavior. I n alatersectionweexamine howthatbasiccellularresponseis generated.Further,theheartconsists ofspecializedregions. Theelectricalactivityof theh ea rt is pacedb yso me oft he se re gio ns,communicatedbyothers,andmodifiedtomatchtheneedsofeachworkingregion. We

will thus also examine thechangeablenatureoftheheart'selectricalactivity.

CardiovasculardiseaseistheleadingkillerofallAmericans, accoun tingformo rethan50 %ofallannual deaths. Thenormalfunction ofthisremarkableorgandepends onit's electricalactivity,andtheinfluence ofthoseelectricaleve ntsoneachofitscells.Whendiseased,itisoftendisturbancesinthatelectrical activity that leadstosuddendeat h.

Inthesesectionswewillexaminethebasicelectrical be havior ofthehea rt.

Cardiac Electrophysiology JoePatlak MedicalPhysiology 301

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Cell-to-cellelectrical transmissionBecauseionsmove freely from celltocell,electricalactivity incardiacce llsistransmittedto theirneighb ors.Cardiacmuscleissaidtoactelectricallyasa“syncytium”.

Consequences:!

!

!

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Excitationproceeds from cell to cell.

Cannotnormallyexcitejustonecell,ora portiono ft heheart .

Cannotadjustcontractionbasedonthenumber ofcells.

Whenoneportionoftheheartisdamaged,thewholeheartcanbeaffected.



Cellular Structure of Cardiac Muscle

Cardiacmusclecomposedofahighlybranchednetworkof small (approx.12X100micron)cells.

Cellmembrane and transverse tubules

Eachcellissurroundedbyathinmembrane--thesarcolemma.Invaginationsofthesarcolemmaformtubules intotheinterior ofthecell.ThesetransversetubulesoccurattheZlinesinventricularmuscle.

Contractile filaments

Striatedappearancecausedbyoverlappingarrayof thick (myosin) and thin(actin) filaments(myofilaments) asinskeletalmuscle.Sarcomeresare basiccontr actil eunits;structureandtermino logy(A band,Ib and,Zli ne,Hzone)sa measinskele talmuscle.

Myofibrils

Thecross-sectionof thecellismadeupofbundlesof aboveproteinfilaments; thebundlesarereferredtoasmyofibrils.

Intercalateddiscs

Finger-likeprojectionsofadjacentcells"lock"cellstogether atintercalateddiscs.Membranesof two cellsarecloselyap posedhere. Thespecialized regioncalledagapjunction,ornexus,allowsionstomovefreelyfromcelltocell,accountingforthelowcell-to-cellresistanc e.

Internal membrane system

TheSarcoplasmicReticulum,orSR,isspecialized

endoplasmicreticulumthatforms a membrane- boundedintracellularcompartment.TheSRis a systemofclosedtubulesandsacs.AtubularnetworkofSR surroundsmyofibrils;enlargedsacs canbefoundwheretheSRcomesclosetothesurfacemembrane(wheretheyarecalledsubsarcolemmal cisternae)or wheretheSRapproachestransversetubules(thesearecalledterminal cisternaeor lateral sacs).


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Sinoatrial (SA) node

Atrial muscle

Atrioventricular (AV) node

The , is located atthejunctionofthesuperiorvena cavaandtherightatrium.TheSAnodeservesasthenormalpacemakeroftheheart,initiatingeachnewwaveofexcitation.

Activityisconductedthroughatrialmuscletoexciterightandleftatria.Therearepreferentialconductionpathways--

thatconduct activity rapidly from the SA tot he AVn od e(s ee below). conductsacti vityfromtherighttotheleftatrium.

TheAV nodeis located atthebaseoftheinteratrialseptum,neartheopeningofthecoronarysinus.Itconductselectrical activity from theatr ia tot he bu nd le ofH is( see below). Electrical conduction int h e AV no de is ve ry sl ow(approx.0.05mm/ms); this ensures a delaybetweenactivationoftheatriaandactivationoftheventricles.

sinoat rialnode,orSAnode

anterior, middle,andposteriorinternodal tracts

Bachmann's bundle

Ventricular conducting system

Components, gross organization

Structure

Theventricularconductingsystem includesthe

.TheAVnodemergeswiththeBundleofHis,whichisthefirstpartofasystemthatconductselectrical activity intotheven tricl es.T heBu ndle ofHisenterstheinterventricularseptum,whereit subdividesintothe ,whichactivatethe left and rightventricles. Inbothventricles,t heventricularconductingsystem branches extensivelyto

becomethe . Th es ec el ls ar et he on lyonesofthissystemthatactuallymake electricalcontactwithventricular cells.

Cellsoftheventricularconductingsystem arelarge,andspecialized for rapidconduction. Thesecolumnsof electrically excita blecells( shownatt heright)a resurroundedbythicksheathsofconnectivetissuewhichinsulatesthe excitablecells from the surroundingventricularmuscle.

BundleofHis(alsocalledtheAVbundle,the Hisbundle,or thecommonbundle),bundlebranches,andPurkinje system

left andrightbundle branches

Purkinjefibers

Sequence of ventricular

activation

AsthewaveofelectricalexcitationleavestPurkinjefibers,it spreads to the ventricular muscleinmanyplacessimultaneouslysothathe ventriclescanbestimulatedasquicklya possible. Nevertheless,thereisastandardsequencebywhichtheexcitationpassesthroughtheventricles. First, theventricular

septumisstimulated. Next, thea pe xo ft heheart,andthenexcitationspreads upwardstowards thebase. Ingeneral, the ventriclesare stimulatedontheirendocardialsurface,andtheexcitationspreads throughthewalltthe epicardium. Remember: Apexbefore

Base,EndocardiumtoEpicardium.

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Basic Activation Sequence:SA Node Atria AV Node Bundle o f His Purkinje System Ventricles



Cardiac Action Potentials, Fast and Slow

Ventricular Muscle

RestingPotential:

FastActionPotentials:

Therestingmembranepotential of ventricularmuscleis-80mVto-90mV,associatedwithahighKconductance. Inhealthyventricularmuscle,theresting potentialis stab leandd oesnot changeuntilthemuscleisgivenanadequatestimulus.

Theactionpotentialofventricular muscleis quitedifferentfrom that ofanerveor

skeletal muscle. Whi le itd oe sha ve arapidupstrokeandovershoot,likeinanerve,therepolarizationis muchmore prolonged(hundredsof ms),withanextendedplateauatabout0mV.

CardiacActionPotentials

RestingPotentials

Slow Phase0: SANode,AVNodeFast Phase0: Atria,ConductingSystem,Ventricles

DiastolicDepolarization: SA Node ,AVN ode ,Bun dleo fHStableRestingPotential: Atria,PurkinjeFibers,Ventricles

Overall,ventricularpotentialscanbedescribedbyfivephases,0-4.

Phase0:

Phase1:

Phase2:

Phase3:

Phase4:

Aninitialrapiddepolarizationoccursshortlyafteranadequatestimulus.Themembranevoltageactuallychangessignwithin1-2ms;attheendofthisinitialdepolarizationthemembranevoltageisapproximately +30 m V. This initial rapi dde pola riza tion isre ferr edto asp hase 0,a ndi scau sed bya rap idincrease inNa conductanceof themembrane.

Aninitialrepolarizationnext occursthatpartiallyrepolarizesthecellmembranetoa voltagenear zero.This portionoftheactionpotentialiscalledphase1. Phase1iscausedbytheinactivationofNachannelsandthetransientopeningof Kchannels.

Afterphase 1,repolarizationslowsdramaticallytoformtheplateauorphase2ofthecardiacaction potential.Durin gtheplateau,thecellsrepolarizegradually for100-200ms. The plateau isprimarilydominated byCaconductance. Thisistheper iodwhent heve ntricl es cont ract.

Astheactionpotentialcontinues,repolarizationacceleratestobringabout finalrepolarization,or ph as e3.P ha se3b ring sthe me mbrane po tent ialbac kt ot herest ingp ot en tial . Ph as e3 is ca us ed pr imar il yb yincreased K conductanceofthemembrane

Theintervalbetweenactionpotentials,whenthemembranepotentialofaventricularcellisattherestingpotential,isoftencalleddiastoleorphase4.(Thevoltageisstableduringdiastoleinventricularandatrial cells; inothercardiaccellsgradualdepolarizationmayoccurduringdiastole.) Duringphase4theK conductanceofthemembraneishigh.


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SAandAVNodePotentials:

ActionPotential:

RestingPotential:

Theactionpotential oft he SA No de (a nd th eA Vn od e) ha sa ve ry di ff er en tf or mfromthatofventricular muscle. Phase 0isslo wer,the peakpotential isnotasgreat,andthereisnomarkedplateau. Repolarization(Ph ase3)g radual ly

occursfrom peakba ckt ore st.

Unlikeventricularmuscle,therestingpotential ofnodaltissuesisnotstable. The potentialis most negativeimmediatelyfollowinganactionpotential,butgraduallydepolarizesuntilthethresho ldfora newac tionpo tentia lis reached. This“diastolicdepolarization”is duetotheactionof cation ch ann els (ca lle dI, mai nly Napermeable)

duringPhase4andagradualdecreaseintheK conductance.

f


Measuresthedistance thatthespreadingexcit ationcoversinagivenamountoftime.Itisprimarilydeterminedby:

Conduction velocitychanges inthedifferentpartsoftheheart.

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!

!

!

!

!

Cell diameter

dV/dtofupstroke

Amplitudeofthe upstroke

ConductingSystem(BundlesandPurkinjeFibers)

Atrial and ventricularmuscle

AV node

:Thetissue'sinternalresistanceisinverselyproportional todiameter.

:Fastupstrokedepolarizes adjacentcellstothresholdquickly.Fast actionpotentials

will b econductedfasterthanslowactionpotentials.

:Largeamplitudeactionpotentials(e.g.ventrical muscle) producelargevoltagedifferencebetweenactiveandadjacent resting cells.

: Largecells,fastupstrokes,largeovershoots causeveryrapidconductionof2-5mm/ms.

: Intermediateconductionvelocityofabout 1 mm/ms.

: Very small cells, slowupstrokes,smallovershoots.Conductionvelocityisroughly0.05mm/m

Conduction Velocity

P a g e 5

Ventricular Muscle

AV Node

Refractory Periods

Duringtheactionpotentialofcardiactissues,anadditionalstimuluswillbeincapable ofinitiatinganew actionpotential. Thisis calle dinhe artthe

or ERP. This periodis followedby ab ri ef ti me wh ere ano th er largestimuluscangenerateanewactionpotential--t he orRRP.

Inventricular muscle, theE RP is du et ot heinactivationofNa channels. Itlas ts untilthe endofPhase3.

Innodaltissues,theERPisduetotheinactivationofCachannels. NotethattheirslowrecoverycausestheERPandRRPofthenodestolastlonger thantheactionpotentialitself.

“EffectiveRefractoryPeriod”

“RelativeRefractoryPeriod”

SA Node



The EKG and its relation to the heart's excitation

EKG SignalAmplitudeProportionalto:

+

+

+

+

Amount oftissuechanging potential

Directionofpropagation

compared to theelectrode orientation.

Size of potential change

Speed of propagation

EKG Electrodes andtheirelectricalorientationaroundthe heart:AnEKGcanbemeasuredwithasfewastwo“leads”, i.e.wireswithelectric alcon tactto theski n. However,byconvention,recordingpointsareestablishedatthearmsandoneleg. Whencombinedinvariousways,sixelectricalviewsoftheheartcanbeobtainedthatprovideaverticalcrosssectionoftheexcitation pattern. Inaddition,recordings areoften madefromel ec trodes positionedhorizont allyaroundtheheart,providi ngahorizont al

crosssectionof theheart'sexcitation.All 12“views”arecommonlypresentedtogetherinaprintedEKG.

P a g e 6

I

IIIII

aVF

aVLaV R

V1

V2 V3 V4

V5

V6

Theelectrocardiogram(EKGor ECG)isarecordingoftheheart’selectrical activity asseenfromthesurfaceof thebody.Whencurrents

spreadthroughtheheartasthetissuedepolarizesor repolarizes,small voltagescanbepickeduponthe skin. Theseprovidea critical,non-invasivewaytoviewthehealthoftheheart’selectricalconduction system.

Thissectionprovidesbasic

information aboutwhat you seein anEKG. A secondhandoutdetailsrhythmdisturbancesyou

areresponsibleforrecognising.



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AtrialContraction

Ventricular Contraction

(Systole)

Normal and abnormalvalues for

heartrate

BPM Normal SinusRhythm 60-100Sinus Bradycardia <60SinusTachycardia >100

Relationshipbetween:ActionPotentials and theEKG

ActionPotentials and contraction.

Phases of the EKGcorrespond to cardiacexcitation.

P wave

P-R interval

QRS Complex

Q-T interval

T wave

Spreadofexcitationthroughatria.

AtriaContractExcitationwithinAV node

Spreadofexcitationthroughventricles

VentriclesContractAPphas e2

VentriclesRepolarize



Measuring intervalsand rates in EKG strips:TheEKGisusuallytracedontographpaperataconstantrate. ForstandardEKGtracings,thefollowing apply:

Thelarge and smallboxes canbeusedtomeasureintervalsbetweensegmentsoftheEKG.One largebox=0.2second,eachsmallbox = 0.04 seconds.

Number

of large

boxes

Heart

Rate1 300

2 150

3 100

4 75

5 606 50

Theheart rate(inbeatsperminute,BPM)canbedeterminedquicklybydividing300bythenumber oflargeboxesbetweensuccessiveR-wavepeaks

150

100

75

60

Normal intervals include:+

+

+

PRintervalQRS interval

QT interval

:0.12-0.20sec(3-4smallboxes): 0.08-0.12 sec(2-3smallboxes)

: 0.30-0.46 sec(norma lrange, varieswit hheartra te)

Measuring the Heart Rate

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Ionic Basis for the Cardiac Action PotentialTheactionpotentialsinatrialandventriculartissuesare caused, asinnerve, bythemov ementsofsev eraldifferent ionsthroughspeciallyadaptedchannelsinthe membrane.

Inheart,aricherarrayofionsandchanneltypesisinvolved ingeneratingthe complex signalsneededtosignalandcontrol thecardiaccontraction.

Manyofthedrugsthatmodifycardiacelectrical behaviorare targeted to act onthesechannels. Weare alsobecomingaware ofanu mberof chann elmutationsthatleadtodisruptionofnormalcardiacelectrical stimulation.

Inthissectionwestudytheionsandchannels

involved.

REMEMBER:

TochangeVm, a net current flow.

If Vm ischanging, then a currentisflowing.

Inward Current ==DepolarizationOutward Current=Hyperpolarization

must

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Exampleofcurrentsandgenesresponsiblefor theventricularactionpotential. Fro mNa tur e, V.4 15 ,P215. (simplifieddiag ramo nne xtp age ).



EK

ENa

VM

I

Outward

Currents

Inward

Currents

Whenionchann els areopen,specificcurrents willflowthroughthem. Thedirectionandmagnitu deof thiscurrentdependsonthe“drivingforce”forionicmovement.,andonhowmanychannels areopen.

Drivingforcedependsonthedifferencebetweenthemembrane potential and theequilibrium (Nernst) potentialfor that ion.

If themembranepotential ismorepositivethantheequilibrium potential,thencations like Na a n d K will flowouto fthecell. Ifitismorenegative,theywill flowin.

Noteat righ tt hatdur ingt he en tireca rdiaca ct ion potential(superimposed),Kcurrents areou tward,while Nacurrentsare inward.

Ion currents depend on membrane potential

Ion currents during the ventricular action potential


Time

ICa

INa

IK

EK

ENa

ITO

IK1

VM

0

1

2

3

4

}} Outward

Currents

Inward

Currents

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Duringtheactionpotential,depolarizationiscausedbyinwardcurrents,andrepolarizationdue tooutwardcurrents.

ThefastNacurrentgives thepowerfulinitialdepolarizationinphase0,whilethe slowercurrentsthroughtheL-typechannel maintain that depolarizationthroughtheplateau.

Severaldifferent K currentsmediatedifferent phasesof repolarization: A fatransientcurrentcontributestophase1

andtwoslowercurrents(IK-randIK-scalledheresimplyIK)helpendthe plateau. Finally,t he in ward re cti fyi ngcurrent,IK1,ishighduringphase4,anlow during theactionpotential.



Thefollowing table summarizes theioniccurrents thatplay an importantrole i nthecardiac action potential. Each currentcorresponds to a different channel type,withthe gating andpermeability properties as shown:


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Long QT Syndrome

Whenphase2oftheactionpotentialisprolonged,thenthereisanincreaseddelaybetweendepolarizationandrepolarizationof theven tricle s,i.e .alo ngQT segme nt. If Naor Cac urr en tsare increased (or don’tinactivateat theirnormalrates),oriftheKcurrentsdon’tturnonsufficiently, thentheventr icular cellswi llstayl ongera ttheirp lateau .

Thisconditioncanbeacquiredviadrugtoxicityor

There area numbe rofdiff erent formsof familialdominant disease, causedbymutations incardiacionchannels:

LQT-1 -->IK-sLQT-2 -->IK-r LQT-3 -- >IN a

Thechart below illustrateshow a familial patternofdisease wasdiscoveredfollowingsuddendeathofachild.(ClinicianReviews,V.13#1,P.40).

electrolyteimbalance. However, it isnowrecognizedthatfamilials tothisdiseaseisnotrare. Approximatelyoneinevery5000personsmayhavevariationsinchannelstructurethatgiverise to thiscondition,anditappearstocause3000to4000suddendeathsinchildrenandyoungadultseachyear.

!

!

!

usceptibility

QT>0.46s

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Time

Time

AfterParasympathetic

After Sympathe

Stimulates

Stimulates

Gs Gi

If

ICa


SA Node, rate > 60

AV J unction, Rate 40-60

AtrialFoc i,rate60-80

VentricularFoci, rate 20-40

Pacemakecurrents and AutonomicControl of the Heart:

Severaltissues inthehea rtnorm allyh ave anunstableresting

potential(diastolic depolarization)duringphase 4. Thisisdueprimarilyto thepresenc e ofthePacemaker current, I ,

whichisactivateduponhyperpolarizationfollowingphase3oftheactionpotential.

Stimulation o ft he causescyclic-AMP production,w hi ch le ad st oth est im ula ti ono fI and the

inhibition o f I . Diastolicdepolarizationbecomessteeper,

andtheheartreachesitsnextthresholdmorequickly.

Conversely, stimulationoftheincreasesI,whichslowsdepolarizationbyopposingI.

Sympat hetics innervateall portionsof theheart.T heyincreaseautomaticityandstrengthofcontractionthroughoutthe heart.Parasympatheticsinnervateabovetheventricles(SAnode,

atria,a n d AVnode). Theyslowautomaticityinallthesetissues.

f

f

k

k f

Beta-1receptors

Theheartrateincreases.

muscarinicreceptorsThe

heartslows.

OverdriveSuppressionEachactionpotentialresetsthediastolicdepolarizationtoitsmosthyperpolarizedlevel. TheSAnodeisusuallythefastest

pa ce ma ke ri nt he he ar t, so al lt he sl ower pacemakers are r es et by th en od e .Thesesecondarypacemakers thereforedon’normallycontributeextrabeats.

If theSAnodestopspacing(orslowsdramatically),thenasecondarypacemaker cantakeovergeneratingregularheartbeats.Theatriaareoftenthe nexttobeat. If theyslow, t h e AV junction cant a k e o v e ra talowerrate(40-60bpm),oreventhe

ventricles(20-40bpm).

eachbeat

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However,whenventricularorconductingtissueisdiseasedordamaged,itsconductingvelocityslowsdownanditsrefractoryperiodlengthens.

Forexample,this couldmeanthatasegmentofPurkinjetissueisnotreadytoconductthenormalaction poten tialwh enita rrives. However,th at acti on po tent ialc an laterspr eadb ac ki nt ot hi sdam aged ti ssue fromthe ventricle side. Ifthisrev erseprop agation isslow,th enthe "backw ards"sig nalcan arriveb ackinc ontactwithhealthytissue thathealthytissuehasrecoveredfromitsrefractoryperiod.

Inthiscase,thisregionoftheheartrepeatedlystimulatesitself(andtherestoftheheartaswell). This iscalled a ,whichresultsinperiodicactivitygeneratedoutside thenormalpacemaker system(an"EctopicFocus"). Such an area,whenstimulatingat a highr at e ca nl ea d to "

. Ifseveral(ormany)suchregionsbegintotakeoverstimulationontheirown,thecardiacelectrical behavior becomeschaotic. Thisiscalled" ",whichcanoccurineithertheatriaortheventricles.

AFTER

reentrantrhythmVentricularTachycardia"

or"Atrial Flutter"fibrillation

Theactionpotentialconductionthroughtheventricalsisfastenoughsothatallpartsoftheheartare normallystimulated andin their refractoryperiodsatthesametime. ThelongERPoftheAVnodealsopreventstheventricularaction potentialf romreexcitingtheatria.

Reentrant Rhythms

ReentrantRhythminAtrial Flutt

Theestablishment ofacir cularp atteofactivitywithintherightatriumisshown. Conductionveloc ityi sslowenoughheretopermitpartsoftheatriatorepolarizewhileothersarestillactive. Theactivationproceedsin a circle(inthiscasearoundtherightatrium).

Duringsomecycles,theAVnodeisrepolarizedandreadytoconduct. Tventriclesarethusstimulatedviathe

normalpathway(narrowcomplex).However, the AVnode staysrefractory for severalcycles.

TheEKGshowsregular,fastPwavsuperimposedonamuchslowerQRTpattern.

PWaves

AV Noderefractor eriods

[Illustrationsfrom

www.blaufuss.org]


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?

?

?

?

?

?

?

A. Anactionpotentialdepolarizesthe surfacemembraneof thecardiaccell.B. Thesurfacemembraneinvaginates atthelev eloftheZlin esinventri cularmuscle toformtrans verse

tubules(t-tubules).Asthesurface membranesurroundingat-tubuledepolarizes,themembraneofthetubuledepolarizes.

C. Duringthep lateauofth ecardiac actionpote ntial,calc iumchann elsinthesarc olemma and t-tubulesopen.Calciuminfluxthroughthesechannelsprolongstheplateau(phase2)oftheactionpotential.Becauseintracellularcalcium is extremelylow a tthe beg inni ngof the actionpotential,thisinflu xalsoslightly

increases theintracellularcalciumconcentration.D. Theslight riseofintracellularcalcium causedbyICat rigg ersth erele aseo fadd ition alca lcium fromt he

SarcoplasmicReticulum. Therel easetake s placethroughspecia lcalci umrelea sechan nels (ryanodine-sensitive)intheportionoftheSRmembrane thatfacesthet-tubularorsarcolemmalmembrane.

E. Calcium diffusestothe myofilamen ts,andbin dstocalci umbinding sitesontropo ninC,act ivatingcontraction.Someof thiscalcium wasderive dfromCa entryv iaICa, butmost wasrele asedfro m theS R stores.

F. TheSRmembranecontain high-affinityATP-drivenCapumps.Th eseuseATPtoprovide theene rgyfo r "uphill"transportof Cafromthemy oplasmintot heinterioro ftheSR.Asth esepumpsre ducemyo plasmiccalcium,calciumdissociates from troponinC,endin gcont raction.

G. Asodium-calciumexchanger(antiporter)is primarily responsiblefor extrudingCa;t hisexch anger

allows3Na+toenter,downthesodiumconcentrationgradient,inexchangeforextrusionofonedoublychargedCaion.AnATP-utilizingCapumpinthesarcolemmaalsoextrudesCa;thispumphasalower capacitythanthesodium-calciumexchanger.

Excitation-contraction couplinginventricular muscle.

Excitation-contraction coupling is theprocesswherebythesurfacemembraneactionpotentialiscommunicatedtothemyofibrilstructuresthatcausethe contraction. Although similar to the process in

skeletal muscle,therearesomeimportantdifferences.

EC-Coupling Sequence:



Important functionaldifferences betweencard iac and skeletal ECcoupling.

?

?

?

Caentryandextrusion:

Carelease mechanismdifferent:

Carelease not normally sufficienttosaturatetroponin:

About10% ofthetotalriseinintracellularCaentersviaCachannelsduringeach cardiacactionpotential.This amount,byitself, isnotenou ghtoful lyactiva tethemy ofilament s, bu ti ti sreq ui redt or ep leni sh thei nt ra ce ll ul ar Cast or es that do pr ov id emos toft he ca lc iumf or activation (seediscussionbelow o nth eCa po ol) .

CardiacmusclereleasesCabya"calcium-inducedcalciumrelease" mechanism.Thismechanism staysrefractoryfor a timeaf tere ach rele ase .Th isis why the cel ls

cannot producesustainedtetaniccontractions.In cardiaccellscontractingundernormal

conditions,theamountofCareleasedwitheachstimulusisnotsufficienttoactivatethemyofilamentsfully.IfthecalciumcontentoftheSRrises,Careleasecanincrease,andcontractioncanincrease.

Ca extrusiona n d t he early afterdepolarization:Caleavesthecytoplasmaftereachbeat(duringphase4)viapumpsthatreturnittothesarcoplasmicreticulum,andvia extrusion fromthe cell usingprimarilytheNaXCaexchanger.

TheNaXCaexchanger iselectrogenic. Thre eNa’sf lowin tothe cell

for eachCathatleaves,leadingtoane tinward(depolarizingcurrent). IfCalevelsinthecytoplasmbecometoohigh(theCa pool),thisNaXCadepolarizationcanbringt hecelltothreshold,andstimulateasecondAPjustafterthefirst. Inthesubsequentbeats,theCaloadbecomes evenhigher,becausephase4was muchforeshortened. Thise ffec tcansetupra pidrep eatso factio n potentials.

Such “delayedafterdepolarizations”are important sourcesof ventriculartachycardia,andcanleadtosyncopeorsuddendeath.


Ca-activatedCa release

Inskeletalmuscle,theSRCa-releasechannel isactivatedbythevoltagesensorsofaT-tubuleCachannel. Inheart,it is theCathatentersthrough

the L-typeCachannelthat stimulatesrelease. This iscalledCa- activatedCarelease.

CathatisreleasedfromtheSRhelpsenhanceopeningofotherreleasechannels. Thismakesth e Carelease“all-or-nothing”, muchl ikeana ct ion potential. It alsohasinactivationanda refractoryperiod!

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Autonomic Adjustment of

ContractionSympatheticandParasympatheticstimulation alters the strengthandspeedofcontractionintwoways.First,bychangingtheheartrate,the

sizeoftheCapoolchanges.

Second,theactivationofsympatheticBeta-1receptorsleadstothe productionofcycli c-AMP. ThissecondmessengeralsoalterstheSR andthecontractileproteins to further enhancecontractionstrenght. Thislattereffectis called an increa seintheheart’s “contractility”.


The Ca PoolAlltheCawithinthecell(withintheSRandfree)constitutetheCapo ol. Duringdiastole,mostofthisCaissequesteredwithinthe SR andtheheartisre laxed. Duringsystole,thisCaisfree,anddeterminesthe strengthofcontraction. ChangesintheCapoolthusdeterminethestrengthofeachbeat.

ThesizeoftheCapoolultimatelydependsonthebalance betweenCaentrydu ringph ase2a nditsextrusionduringphase4. At fasterheartrates,theCapoolincreasesbecausethere islesstimebetween be at st oe xt ru de th eC a. Th eh ea rt bea ts ha rd er an df as te rd ue to th is la rg er Ca po ol .

At hi gh he art rates,theactionpotentialshortens du etot hish ighC apo ol. ThisadaptationhelpspreventCaoverloadathighheartrates.

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cardiac hand

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