Effect of forskolin on action potential, slow inward current and tension of frog atrial fibers.

The new nonhormonal activator of adenylate cyclase forskolin was studied on frog atrial trabeculae by current clamp and voltage clamp methods using a double sucrose gap technique. Forskolin (5 X 10(-6) M to 2 X 10(-5) M) dose-dependently increased action potential duration, the height of the plateau and twitch tension. The time constant for inactivation of the slow inward current and the steady state kinetic variables of calcium channels d infinity and f infinity remained uneffected. Forskolin increased the amplitude of slow inward calcium current isi and of the phasic tension related to it. The maximal conductance gsi increased. These effects were indistinguishable from those obtained earlier on cardiac fibers with hormonal and nonhormonal activators of cyclic AMP-dependent phosphorylation. The beta-adrenoreceptor antagonist propranolol 10(-6)M did not decrease the effect of forskolin. Forskolin had no effect when slow inward current was previously increased by saturating concentrations of the beta-adrenergic agonist isoproterenol (10(-4)M). Our results are in favour of the hypothesis that cyclic AMP-dependent phosphorylation of membrane proteins modulates the Ca-entry in the heart cells through the membrane slow calcium channels.