Modulation of manganese currents by 1, 4-dihydropyridines, isoproterenol and forskolin in rabbit ventricular cells.

Although often used as a Ca(2+) channel blocker, Mn(2+), in fact, permeates through Ca(2+) channels. Under Na(+)-free conditions, depolarizing pulses evoked slowly-decaying Mn(2+) currents ( I(Mn)). Maximal I(Mn) densities in the presence of 5 and 20 mM Mn(2+) were 0.42+/-0.12 pA/pF (mean+/-SEM, n=17) and 1.23+/-0.10 pA/pF ( n=40), respectively. At 5 mM, the ratio of maximal amplitude of I(Mn) to that of the Ca(2+) current ( I(Ca)) was 0.079+/-0.009 ( n=8). I(Mn) elicited from a holding potential of -50 mV was depressed by nitrendipine (1 microM) by approximately 70%. Nitrendipine (0.3 microM) shifted the steady-state inactivation curve to more negative potentials and shifted the potential for half-maximal inactivation ( E(0.5)) from 1.3 to -8.8 mV and also decreased the time constant of decay of I(Mn) at 20 mV from 986.2 to 167.9 ms. BAY K 8644 (1 microM), isoproterenol (10 microM) and forskolin (10 microM) all increased I(Mn) and shifted the current/voltage ( I/ V) relationship to more negative potentials. The small, slowly-inactivating I(Mn) is thus modulated by dihydropyridine Ca(2+) channel modulators and cyclic AMP-mediated phosphorylation in a manner similar to other L-type Ca(2+) channel currents. L-type Ca(2+) channels are involved in the regulation of intracellular [Mn] in ventricular myocytes.