Mg(2+)-dependent facilitation and inactivation of L-type Ca(2+) channels in guinea pig ventricular myocytes

Abstract

This study aimed to investigate the intracellular Mg(2+) regulation of the L-type Ca(2+) channels in guinea pig ventricular myocytes. By adopting the inside-out configuration of the patch clamp technique, single channel currents of the L-type Ca(2+) channels were recorded at different intracellular Mg(2+) concentrations ([Mg(2+)]i). At free [Mg(2+)]i of 0, 10(-9), 10(-7), 10(-5), 10(-3), and 10(-1) M, 1.4 μM CaM + 3 mM ATP induced channel activities of 44%, 117%, 202%, 181%, 147%, and 20% of the control activity in cell-attached mode, respectively, showing a bell-shaped concentration-response relationship. Moreover, the intracellular Mg(2+) modulated the Ca(2+) channel gating properties, accounting for alterations in channel activities. These results imply that Mg(2+) has a dual effect on the L-type Ca(2+) channels: facilitation and inhibition. Lower [Mg(2+)]i maintains and enhances the basal activity of Ca(2+) channels, whereas higher [Mg(2+)]i inhibits channel activity. Taken together, our data from the application of an [Mg(2+)]i series suggest that the dual effect of Mg(2+) upon the L-type Ca(2+) channels exhibits long open-time dependence.

Keywords: Ca(2+) channels; Inside-out configuration; Mg(2+); Open probability; Open time.