The dihydropyridine derivatives CGP 28392 and BAY K 8644 increase calcium current amplitude primarily by markedly prolonging the mean open time of single calcium channels in cultured cardiac cells.
Dihydropyridine derivatives CGP 28392 and BAY K 8644 increase calcium influx in cardiac cells by prolonging the open state of calcium channels, revealing a mechanism distinct from beta-adrenoceptor agonists.
Absolute Event Rate: 23.8% vs 20.9%
The dihydropyridine derivatives CGP 28392 and BAY K 8644 exert a strong positive inotropic effect in mammalian cardiac muscle, presumably by increasing Ca influx during the action potential. Analysis of the drug effects at the level of single Ca channels by means of the patch-clamp method revealed complicated changes in the kinetics of channel gating. The prevailing effect is a prolongation of the mean open time of Ca channels. In addition, the intervals between channel openings can be slightly prolonged. Ensemble averages of single-channel traces showed a concentration-dependent increase in the mean current amplitude by the drugs. In contrast to beta-adrenoceptor agonists, the increase in Ca current by the dihydropyridine derivatives is not associated with an increase in the intracellular cyclic AMP level.
Kokubun et al. (Wed,) conducted a other in Cultured cardiac cells. Dihydropyridine derivatives (CGP 28392 and BAY K 8644) vs. Control (absence of drug) was evaluated on Single-channel slope conductance (pS). The dihydropyridine derivatives CGP 28392 and BAY K 8644 increase calcium current amplitude primarily by markedly prolonging the mean open time of single calcium channels in cultured cardiac cells.