Calcium-mediated inactivation of the calcium conductance in cesium-loaded frog heart cells.

Ca current inactivation was investigated in frog atrial muscle under voltage-clamp conditions. To inhibit the outward currents, experiments were performed on Cs-loaded fibers and in 20 mM Cs (K-free) Ringer with 4-AP added. Inactivation, produced by a conditioning pulse, was measured by reducing the current during a subsequent test pulse. The extent of inactivation increased initially with prepulse amplitude and then decreased as the prepulse potential became progressively positive. Relative inactivation follows a U-shaped curve. When Sr was substituted for Ca, both the degree and the rate of inactivation decreased. Relative inactivation appeared to be linearly related to the amount of divalent cations (Ca and Sr) carried into the cell during the prepulse. Elevating Ca enhanced peak current and accelerated its decline. Elevating Mg decreased peak current and slowed its decline. An application of Na-free (LiCl) solution resulted in a somewhat smaller but faster inactivating current. Adrenaline increased and D600 decreased the maximal Ca conductance with little alteration in the inactivation rate; Co decreased both peak current and the rate of inactivation. Enhancement of the outward currents, reduced driving force, and intracellular surface charge screening do not adequately account for the above results. Evidence was considered that Ca entry mediates most of Ca current inactivation in frog atrial fibers. Removal from inactivation was also investigated in normal-Ca, Ca-rich, and Sr solutions. Recovery after partial inactivation by high depolarization was biphasic. Recovery was slowed by 10 Ca and accelerated by 1.8 Sr, whereas opposite effects have been shown on activation.