Ca2+ channel activation by CGP 48506, a new positive inotropic benzodiazocine derivative.

Effects on L-type Ca2+ channels of a new positive inotropic compound, the active (+)-enantiomer of the Ca2+ sensitizer 5-methyl-6-phenyl-1,3,5,6,-tetrahydro-3,6,-methano-1,5-benzodiazocine -2,4-dione (CGP 48506), were studied in guinea-pig cardiomyocytes. Whole-cell currents (physiological solutions, 2 mM Ca2+) were enhanced approximately 1.8-fold (10(-4) M, n = 7). Slowing of (de)activation kinetics became apparent under conditions where K+ currents were fully eliminated and Ca(2+)-dependent inactivation was minimized (n = 7). Single-channel current (70 mM Ba2+) and mean open time were increased approximately 2.5-fold (10(-4) M, n = 5), because the drug specifically enhanced sweeps containing long openings (mode 2). Therefore, CGP 48506 stimulates Ca2+ channels in a manner reminiscent of, but not identical to chemically distinct activators like Bay K 8644.