Preferential loss of EC coupling gradation at positive membrane potentials in rat ventricular myocytes

Rat ventricular myocytes switched from a solution containing 1 mM extracellular Ca to one containing 5 mM extracellular Ca exhibited larger Ca currents that inactivated more rapidly. Their Ca transients exhibited a slower decay. In some cells the amplitude of the Ca transients increased markedly, but not in others. Strikingly, in about half the cells examined, the graded nature of the Ca transients over the range of positive membrane potentials was lost, as were Ca transients elicited upon repolarization. These changes were manifest without equivalent loss of gradation over the range of negative membrane potentials (-35 to 0 mV). Such preferential loss of gradation at positive membrane potentials also occurred in solutions devoid of extracellular and/or intracellular Na, and was abolished by nifedipine. The results suggest that Ca-induced Ca release from the SR at positive potentials can saturate or become regenerative if the Ca entry trigger is increased. The lack of a similar effect at negative potentials indicates that large numbers of activated L-type channels are critical for induction of regenerative behavior.