L-type calcium channels, found abundantly in the heart, are activated when the action potential upstroke reaches approximately −20 mV. These channels allow for a long-lasting Ca++ current and are inhibited by calcium channel antagonists like verapamil, amlodipine, and diltiazem. In contrast, T-type calcium channels, which are less prevalent in the heart, activate at more negative membrane potentials (around −70 mV) compared to L-type channels. They also inactivate more rapidly. Opening of calcium channels leads to an increase in Ca++ conductance (gCa) and calcium current (iCa) during the action potential upstroke. This increase in gCa allows for the influx of Ca++ into the cell during the plateau phase, which is crucial for excitation-contraction coupling. Various neurotransmitters and drugs can significantly influence gCa, with catecholamines enhancing gCa and acetylcholine decreasing it. Catecholamines primarily enhance cardiac muscle contractility by augmenting gCa. During the plateau phase of the action potential (phase 2), the concentration gradient for K+ across the cell membrane is similar to that in phase 4, but with a positive membrane potential. Consequently, there is a substantial gradient favoring K+ efflux from the cell. If the gK during the plateau were equal to that in phase 4, the efflux of K+ during phase 2 would surpass the influx of Ca++, preventing the achievement of a sustained plateau.
Fig. 16.6, lower panel) and enable a long-lasting Ca++ current. They are the predominant type of calcium channel in the heart, and they are activated during the action potential upstroke when Vm reaches approximately −20 mV. L-type channels are blocked by calcium channel antagonists such as verapamil, amlodipine, and diltiazem (
Fig. 16.7
T-type (or “transient”) calcium channels are much less abundant in the heart. They are activated at membrane potentials that are more negative (approximately −70 mV) than the potential that activates L-type channels (−20 mV). They also inactivate more quickly than do L-type channels (see
Fig. 16.6 ; compare the upper and lower panels).
Opening of calcium channels results in an increase in Ca++ conductance (gCa) and calcium current (iCa) soon after •Fig. 16.5 Actionpotentialsrecordedfromtheepicardial(Epi)(A), midmyocardial(Mid)(B), andendocardial(Endo)(C) regionsofthefreewalloftheleftventricle.Thepreparationsweredrivenatabasiccyclelength(BCL):thatis,atinterstimulusintervalsof300and8000msec.Thevalueof0mVmembranepotentialisindicatedby“0.”(FromLiuD-W,etal.Circ Res. 1993;72:671.) the action potential upstroke (see
Fig. 16.3 ). Because the intracellular concentration of Ca++ is much lower than the extracellular concentration of Ca++ (see
Table 16.1 ), the increase in gCa promotes the influx of Ca++ into the cell throughout the plateau. This Ca++ influx during the plateau is involved in excitation-contraction coupling, as described in the section “
Various neurotransmitters and drugs may substantially influence gCa. The adrenergic neurotransmitter norepinephrine, the β-adrenergic receptor agonist isoproterenol, and various other catecholamines enhance gCa, whereas the parasympathetic neurotransmitter acetylcholine decreases gCa. Enhancement of gCa by catecholamines is the principal mechanism by which they enhance cardiac muscle contractility.
During the plateau (phase 2) of the action potential, the concentration gradient for K+ across the cell membrane is virtually the same as it is during phase 4; at that time, however, Vm is positive. Therefore, there is a large gradient that favors efflux of K+ from the cell (see
Fig. 16.3). If g
K were the same during the plateau as it is during phase 4, efflux of K+ during phase 2 would greatly exceed the influx of Ca++ , and a sustained plateau could not be achieved.