Inhibition of calcium-dependent action potentials in mammalian myocardium by specific inhibitors of the transmembrane calcium conductivity (verapamil, D 600).

Cat papillary muscles were depolarized from about -80 mV to -50 mV by addition of KCl to Tyrode's solution. This causes an inactivation of the Na-carrying system so that the remaining transmembrane inward current is due, in practice, to Ca. Such action potentials show a reduced rate of rise, a greater overshoot, and a shorter duration. These parameters vary somewhat with the strength of stimulation and, particularly, with frequency. Excitability as well as contractility of the K-depolarized fibers are completely abolished by Ca withdrawal or by addition of verapamil or D 600, which block the transmembrane Ca inward current specifically. Conversely, extra Ca or epinephrine overcomes the verapamil and C 600 effects by increasing the transmembrane Ca influx. As soon as the papillary muscles are returned to Tyrode's solution with normal K0 the Na-carrying system is reactivated. Then Ca withdrawal or Ca-antagonistic compounds lose their inhibitory influence on excitation, whereas excitation-contraction uncoupling persists.