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The application of cyclic-AMP increased the probability of Ca2+ channel inactivation in the absence of external calcium, thereby slowing the membrane time constant (tau) of the current. This effect is dose-dependent (EC50 = 10(-6) M) and is observed with a delay of 0.5-2.5 min. In addition, the time course of inactivation of the Ca2+ channels during step depolarization (in the presence of external Ca2+) was accelerated by the application of cyclic-AMP. The current underlying cyclic-AMP-mediated suppression of calcium channels was determined by the omission of external Ca2+ and the application of various voltage-dependent and nonspecific Ca2+ channel blockers. Cyclic-AMP acted as an open-channel blocker of the channel in the absence of external Ca2+, but it did not decrease the probability of channel opening. Its effect can be fully accounted for by the slowing of the time course of inactivation. 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