Beta-Adrenergic modulation of prepulse facilitation of L-type calcium channels in rabbit ventricular myocytes.

Abstract

It is reported that strong depolarization augments cardiac L-type Ca currents by inducing the special gating mode with long-lasting openings (mode 2) (Pietrobon and Hess Nature 346:651-655, 1990). However, a prepulse to +90 mV did not obviously facilitate the current at 0 mV in rabbit ventricular myocytes as measured in the whole-cell configuration of the patch-clamp method in the presence of 2 mM BaCl(2) in the external solution. In the presence of isoproterenol (1 microM), the inactivation during the prepulse was attenuated, and the prepulse evoked facilitation. However, the current at 0 mV whose amplitude was normalized to the extent of the inactivation at +90 mV still exhibited greater facilitation in the presence than in the absence of isoproterenol. In the cell-attached configuration with 110 mM BaCl(2) in pipettes, repolarization from +110 to +20 mV yielded mainly blank sweeps (mode 0) and only occasionally mode 2, leading to no facilitation of the average current. Isoproterenol augmented the prepulse-induced increase in mode 2, reciprocally inhibited that in mode 0, and increased the fraction of mode 2 in non-blank sweeps after the prepulse. Therefore, beta-adrenergic stimulation favors mode 2 rather than mode 0 at strongly depolarized potentials, thereby promoting the prepulse facilitation and attenuating the inactivation of cardiac L-type Ca currents.