Voltage-dependent modulation of L-type Ca2+ current by manidipine in guinea-pig heart cells

Effects of manidipine, a dihydropyridine derivative, on L-type Ca2+ currents were examined in guinea-pig ventricular cells, using the whole-cell patch-clamp method. At a holding potential of -37 mV, manidipine decreased the Ca2+ current at concentrations above 0.1 nM, and abolished it at 100 nM (IC50 = 2.6 nM). At a holding potential of -78 mV, manidipine did not suppress the Ca2+ current at concentrations less than 100 nM, but increased the Ca2+ current slightly at a concentration of 10 nM. The antagonistic effect of manidipine was significant at concentrations above 100 nM (IC50 = 400 nM). The voltage-dependent effect of manidipine on the Ca2+ current may explain the weak negative inotropism of manidipine in ventricular muscles, and provide an electrophysiological basis for its vascular selectivity.