Fig. 16.10 ) because the magnitude •Fig. 16.10 Typical Action Potentials (in Millivolts, y-Axis). Thesepotentialswererecordedfromcellsintheventricle(A), sinoatrial(SA)node(B), andatrium(C). NotethatthetimecalibrationinB differsfromthatinA andC. Numbersonthecurvesdenotethephasesoftheactionpotential.(FromHoffmanBF,CranefieldPF.Electrophysiology of the Heart. NewYork:McGraw-Hill;1960.) of ito during the plateau is greater in atrial myocites than in ventricular myocytes. As already noted, the duration of the action potential in ventricular myocytes varies considerably with the location of these myocytes in the ventricular walls (see
Fig. 16.5). The i to and iK currents mainly account for these differences. In endocardial myocytes, in which the duration of the action potential is least, the magnitude of iK is greatest. The converse applies to the midmyocardial myocytes. The magnitude of iK and the duration of the action potential are intermediate for epicardial myocytes.
The iK1 current does not participate in the initiation of repolarization because the conductance of these channels is very small over the range of Vm values that prevail during the plateau. However, the iK1 channels contribute substantially to the rate of repolarization once phase 3 has been initiated. As Vm becomes increasingly negative during phase 3, the conductance of the channels that carry the iK1 current progressively increases and thereby accelerates repolarization (see
Fig. 16.3
Restoration of Ionic Concentrations (Phase 4)
The steady inward leak of Na+ that enters the cell rapidly during phase 0 and more slowly throughout the cardiac cycle would gradually depolarize the resting membrane voltage were it not for Na+,K+-ATPase, which is located in the cell membrane (see ). Similarly, most of the excess Ca++ ions that had entered the cell mainly during phase 2 are eliminated principally by a 3Na+-Ca++ antiporter, which exchanges three Na+ ions for one Ca++ ion. However, some of the Ca++ ions are eliminated by an ATP-driven Ca++ pump.
Cardiacionchannelsareconnectedtocellularproteinstoformmacromolecularcomplexes.Thesecomplexesareinvolvedinmodulatingthetransport,membranelocalization,operation,posttranslationalmodificationandturnoverofparticularionchannels.ThecarboxyterminalsofionchannelslinkthemwithseveralintracellularproteinssuchasPDZ(postsynapticdensity,disclarge,andzonulaoccludens-1)domainproteinswhosebindingsitesinteractwithsynapse-associatedprotein(SAP97),syntrophin,andA-kinaseanchoringprotein(AKAP5)amongothers.Differentmacromolecularcomplexesarefoundindistinctcellularlocations,andthisisthoughttounderlieionchanneldistribution.Thevoltage-sensitivesodiumchannel(Nav1.5)islinkedwithsyntrophin/dystrophinatlateralcellmembranesandwithankyrinB,plakophilin-2,andcalmodulin-dependentproteinkinaseIIattheintercalateddisk.Also,differentionchannelscanfoundinthesamecomplex.ThusNav1.5channelsandinward-rectifyingK(Kir2.1)channelscanbeconnectedinacomplex,orchannelosome, withSAP97.ThislinknotonlyaffectsthelocalizationbutalsoallowschangesintheabundanceofKir2.1channelstoproducereciprocalchangesinNav1.5abundance;theconverseisalsoobserved.ThusthecomplexcontainsKir2.1,whichsetstherestingmembranepotential,andNav1.5,whichaccountsforrapidexcitation.Colocalizationofthesetwochannelsthereforeexertsapowerfuleffectonexcitabilityanditsregulationundernormalandpathologicalconditions(arrhythmias).