MULTIPLE MODULATIONS OF ACTION-POTENTIAL DURATION BY DIFFERENT CALCIUM-CHANNEL BLOCKING-AGENTS IN GUINEA-PIG VENTRICULAR MYOCYTES

Effects of extracellular applications of different types of Ca2+ chann el blocking agents (Mn2+, verapamil, and nisoldipine) on action-potent ial duration and membrane currents were studied by the whole-cell patc h-clamp technique in guinea pig ventricular myocytes. Low concentratio ns of Mn2+ (1 mM) and verapamil (1 mu M) prolonged action-potential du ration at 90% repolarization (APD(90)) with a suppressed plateau phase . Increases in Mn2+ (5 mM) and verapamil (5 mu M) shortened APD(90) wi th a further depression of the plateau. Nisoldipine (0.2-1 mu M) short ened APD(90) without lengthening it. Applications of Mn2+ and verapami l suppressed amplitudes of the L-type Ca2+ current (I-Ca), the delayed outward K+ current (I-K), and the inward rectifier K+ current (I-K1). Furthermore, the ratios of I-Ca:I-K inhibition were similar by low an d high concentrations of Mn2+ and verapamil. Nisoldipine selectively s uppressed I-Ca without effect on I-K and I-K1. A low concentration (1 mM) of Mn2+ not only decreased the peak amplitude of I-Ca but also del ayed its decay time course, which caused an increase in late I-Ca ampl itude at the end of a 200-ms depolarizing pulse. Both verapamil and ni soldipine suppressed peak I-Ca without affecting its decay. Whereas Mn 2+ suppressed I-Ba without changing its decay time course, verapamil a nd nisoldipine speeded up the I-Ba decay with suppressed amplitude of I-Ba. We conclude that different types of Ca2+ channel blocking agents (Mn2+, verapamil, and nisoldipine) diversely modulate APD because of their multiple modes of actions on I-Ca and I-K.