Inactivation of calcium channel current in rat uterine smooth muscle: evidence for calcium- and voltage-mediated mechanisms.

Ca channel currents were recorded in Cs-loaded myometrial strips from pregnant rats after addition of tetraethylammonium chloride and 4-aminopyridine (10 mM each) by means of a double sucrose-gap technique. During a depolarizing pulse, the decay of Ca channel current was slowed down when external Ca was replaced by Ba or Sr. This decay represented an inactivation phenomenon, as assessed by the decreased amplitude of inward tail currents following progressively longer depolarizations, the absence of shift in peak conductance curves against membrane potential, and the stable value of the reversal potential when Ba current was increased during conditioning pulses. Inactivation of Ca and Ba currents through Ca channels was studied using the double-pulse method. Conditioning pulses that produced maximal Ca current induced maximal inactivation; with stronger depolarizations, inactivation decreased but was not completely prevented at the expected Ca reversal potential. Increasing the amount of Ca entering the cell during the pre-pulse reduced both amplitude and kinetics of test Ca currents. These results were not observed with Ba as charge carrier suggesting the participation of different mechanisms in inactivation. With Ca as charge carrier, increasing the external Ca speeded the rate of inactivation. This was not observed with Ba outside. Addition of Co (2.5 mM) reduced the amplitude of both Ca and Ba currents but slowed the inactivation of only the Ca current. Recovery from inactivation was described as a two-exponential process only when the conditioning pulse elicited a Ca inward current. In all other cases, recovery from inactivation was represented as a single exponential curve. It is suggested that inactivation of Ca channels in rat uterine smooth muscle is mediated by both internal Ca-dependent and potential-dependent mechanisms.