Potentiation of the calcium-channel currents of internally perfused mammalian heart cells by repetitive depolarization.

The Ca2+ current of single ventricular cells perfused internally by the suction-pipette method can be increased ("potentiated") progressively with repeated stimulation. In Na+- and K+-free external solution containing Ca+, the potentiation response begins to appear at a step potential to -20 mV from a holding potential of -90 mV, reaching a maximum at 0-10 mV. Thus, maximal potentiation coincides with peak inward Ca2+ current. The time course of potentiation development and decline is very slow, occurring in seconds; the former is voltage-dependent, whereas the latter is not. Concomitant with the peak current increase, current decay during the pulse is slowed markedly, thus resulting in the persistence of significant Ca2+ influx at the end of the pulse. With nonperfused single cells, a similar stimulation protocol elicits a similar increase in cell contractility. It is concluded that the Ca2+ channel, after being opened by a single step depolarization, can be opened further by repeating the same step at an appropriate frequency. This additional channel opening is likely to be responsible for the generation of the positive force "staircase" of the myocardial cells in response to increased heart rate.