The voltage- and time-dependent effects of (-)-verapamil on the slow inward current in isolated cat ventricular myocardium.

The effects of (-)-verapamil on the slow inward current in cat papillary muscle were investigated under voltage clamp conditions. The following results, which correlate significantly with the negative inotropic effect of the drug, were obtained: (-)-verapamil reduced the slow inward current in a highly frequency dependent manner, with greater reduction at higher frequency; at cycle intervals longer than 10 sec, the inhibition practically disappeared. As an associated phenomenon there was a stepwise decrease of slow inward current subsequent to an increase in frequency. This "staircase" of the current was facilitated with lowering the holding potential and was diminished by hyperpolarization. Possible mechanisms underlying the membrane action of (-)-verapamil are discussed.