Regulation of the Na-conducting Ca channel during the cardiac action potential

This paper describes the kinetics of an Na-conducting channel during spontaneous action potentials in beating heart cells and during simulated action potentials driven from the patch when the cell is not beating. Since the channel conducts Na only in Ca concentrations below 10(-6) M, and since it is insensitive to tetrodotoxin and has a conductance of 100 pS in 133 mM Na, we identify it as the Ca channel conducting Na in zero Ca. By comparing the channel in beating and nonbeating cells, but under conditions in which it experiences the same voltage in both cases, we observe that: open-channel conductance is the same in beating and nonbeating cells; the channel reversal potential is 25 mV in beating cells and 50 mV in nonbeating cells; the average current peaks later in beating cells than in nonbeating cells, and it has a different time course in the two cases that is not explained by the shift in reversal potential alone; and the average Na current through Ca channels in beating cells peaks much later during the action potential than we would expect if the channel were carrying Ca. We conclude that when the Ca channel conducts Na, its kinetics and reversal potential are strongly influenced by cytoplasmic factors that accompany beating, and that its behavior is not governed by voltage alone. We also conclude that when the Ca channel conducts Na, not only are its reversal potential and conductance altered from what they would be were the channel carrying Ca, but also the channel's kinetics depend on the permeant ion. Since only the channels in the patch are in zero Ca and are conducting Na, while the Ca channels surrounding the patch are in 1.5 mM Ca and are conducting Ca, our data support the idea that it is only the Ca passing through individual channels that influences the kinetics of those same channels.