During the action potential in a cardiac cell, different phases are generated by various ionic currents and channels. In phase 0, both the chemical and electrostatic forces facilitate the entry of Na+ through fast sodium channels, resulting in the upstroke. Phase 1 is characterized by the efflux of K+ through transient outward current (ito) channels, leading to early partial repolarization. In phase 2, the net influx of Ca++ through calcium channels is balanced by the efflux of K+ through inward rectifying current (iK), inward rectifying current (iK1), and ito channels, contributing to the plateau. Phase 3 is dominated by the chemical forces favoring the efflux of K+ through iK and iK1 channels, surpassing the electrostatic forces favoring the influx of K+ through the same channels. Finally, in phase 4, the slight predominance of the chemical forces promoting the efflux of K+ through iK and iK1 channels over the electrostatic forces supporting the influx of K+ through the same channels leads to the stabilization of the resting potential. The currents and channels involved in these phases are depicted in Figures 16.3 and 16.4, respectively. Moreover, the plateau is initiated by the entry of Ca++ through calcium channels, which exhibit slower activation and inactivation kinetics compared to fast sodium channels. During phase 2, the influx of Ca++ is counterbalanced by the efflux of K+ through channels primarily conducting ito, iK, and iK1 currents. The ito current contributes to phase 1 but remains partially active until after phase 2. The entry of Ca++ into the cell is regulated by voltage-dependent calcium channels, including L-type and T-type channels. L-type channels inactivate slowly once open. These concepts are illustrated in Figure 16.6.
Fig. 16.5) because the density of i to channels is less in these cells. The notch is also less prominent in the presence 4 Chemical Electrostatic 3 2 1 0 Fast Na+ Channel Na+ Na+ – – – – – – – – – – – – – – – – – – – – K+ Channel (ito) K+ K+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + Ca++ Ca++ Ca++ K+ K+ K+ Channels (iK, iK1) K+ K+ – – – – – – – – – – – – – – – – – – – – K+ Channels (iK, iK1) K+ K+ – – – – – – – – – – – – – – – – – – – – 0 1 3 4 2
K+ Channels (iK, iK1, ito) •Fig. 16.3 Principal Ionic Currents and Channels That Generate the Various Phases of the Action Potential in a Cardiac Cell. Phase 0, ThechemicalandelectrostaticforcesbothfavortheentryofNa+ intothecellthroughfastsodiumchannelstogeneratetheupstroke.Phase 1, BoththechemicalandelectrostaticforcesfavortheeffluxofK+ throughtransientoutwardcurrent(ito)channelstogenerateearly,partialrepolarization.Phase 2, Duringtheplateau,thenetinfluxofCa++ throughcalciumchannelsisbalancedbytheeffluxofK+ throughoutwardrectifyingcurrent(iK),inwardrectifyingcurrent(iK1),anditochannels.Phase 3, ThechemicalforcesthatfavortheeffluxofK+ throughiKandiK1channelspredominateovertheelectrostaticforcesthatfavortheinfluxofK+ throughthesesamechannels.Phase 4, ThechemicalforcesthatfavortheeffluxofK+ throughiKandiK1channelsveryslightlyexceedtheelectrostaticforcesthatfavortheinfluxofK+ throughthesesamechannels.
0 1.5 3 4.5 10 msec pA Channel #1 current Channel #2 current •Fig. 16.4 Current (in Picoamperes [pA]) Through Two Individual Sodium Channels in a Cultured Heart Cell, Recorded With the Patch Clamp Technique. Membranevoltagewasheldat−85mV,thenabruptlychangedto−45mVatthetimeindicatedbythearrow, andheldatthispotentialfortheremainderoftherecord.(RedrawnfromCachelinAB,etal.J Physiol. 1983;340:389.) of 4-aminopyridine, which blocks the potassium channels that carry ito.
Genesis of the Plateau (Phase 2)
During the action potential plateau, Ca++ enters myocardial cells through calcium channels (described in next paragraph) that activate and inactivate much more slowly than the fast sodium channels do. During the flat portion of phase 2 (see
Figs. 16.1 16.3), this influx of Ca ++ is counterbalanced by the efflux of K+ . K+ exits through channels that conduct mainly the ito, iK, and iK1 currents. The ito current is responsible for phase 1, as described previously, but it is not completely inactivated until after phase 2 has expired. The iK and iK1 are described later in this section of the chapter.
Ca++ enters the cell via voltage-regulated calcium channels, which are activated as Vm becomes progressively less negative during the action potential upstroke. Two types of calcium channels (L-type and T-type) have been identified in cardiac tissue. Some of their important characteristics are illustrated in
Fig. 16.6 . L-type channels are so designated because once open, they inactivate slowly (see