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