Effects on L-type Ca 2 + channels of a new positive inotropic compound, the active (+)-enantiomer of the Ca 2 + sensitizer 5-methyl-6-phenyl-1,3,5,6,-tetrahydro-3,6,-methano-1,5-benzodiazocine-2,4-di one (CGP 48506), were studied in guinea-pig cardiomyocytes. Whole-cell currents (physiological solutions, 2 mM Ca 2 + ) were enhanced 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 Ba 2 + ) and mean open time were increased 2.5-fold (10 - 4 M, n = 5), because the drug specifically enhanced sweeps containing long openings (mode 2). Therefore, CGP 48506 stimulates Ca 2 + channels in a manner reminiscent of, but not identical to chemically distinct activators like Bay K 8644.