CALCIUM CURRENT REACTIVATION AFTER FLASH-PHOTOLYSIS OF NIFEDIPINE IN SKELETAL-MUSCLE FIBERS OF THE FROG

1. L-type calcium currents were activated by depolarization of cut mus cle fibres of the frog. The current was blocked by the dihydropyridine compound nifedipine (5-10 mu M) and reactivated by flash photolysis o f the drug. 2. In the presence of nifedipine, increasing the time inte rval between the onset of depolarization and the flash resulted in pro gressively faster kinetics of the flash-induced current. This change d eveloped with a slow time course similar to that of normal current act ivation. 3. A fast gating mode of the normally slow L-type channel was induced by conditioning activation (500 ms prepulses) applied 80 ms b efore a test step to the same potential. After block by nifedipine, fl ash-photolysis was carried out 40 ms before the end of the long condit ioning pulse. The flash-induced current had the same rapid time course as the current activated by the subsequent test voltage step. 4. Simi larly, the time course of current activation was comparable for the vo ltage-induced fast mode activation (flash applied 5 ms before the test step) and the flash-induced activation 40 ms after the onset of the t est depolarization. 5. Our data suggest that in frog skeletal muscle n ifedipine inhibits calcium current activation by blocking a rapid chan nel gating step while the slow conformational change that normally lim its the rate of activation of the L-type calcium channel remains unaff ected. UV flash illumination results in a fast reactivation indicating that the channels need not be inactivated to be blocked by nifedipine .