Studies on the inhibitory effect of verapamil on the slow inward current in mammalian ventricular myocardium

Abstract

In isolated papillary muscles of guinea pigs and cats the effect of verapamil on the slow inward current was studied by analyzing the slow response action potential (elicited after inactivation of the fast Na system) and in voltage-clamp experiments. 1. (1) Verapamil (4.4 × 10 −6 m) abolished the slow response action potential. An increase of the external Ca concentration from 2 m m to 4 m m partially restored the slow response action potential. Upstroke velocity and overshoot were significantly smaller in the range of the Ca concentrations tested (4 m m to 10 m m) than those values obtained in the absence of verapamil. Verapamil increased the slope factor of the regression line between overshoot and the logarithm of Ca concentration. 2. (2) The verapamil-induced blockade of the slow response action potential was prevented by isoproterenol (9.2 × 10 −6 m). The absolute values of overshoot and upstroke velocity obtained in the presence of isoproterenol were significantly smaller after treatment with verapamil. 3. (3) Verapamil (2.2 × 10 −6 m) decreased the maximum slow inward current by about 50% and shifted the current-voltage relationship over a broad potential range to weaker currents. This occurred in four out of eight experiments without any changes of the time course of the current. On average, time to peak current rose by a factor of 1.4, and the time constant of decay by a factor of 1.25. 4. (4) Verapamil reduced the maximum slow inward tail current indicating a decrease of conductance ( g si ). 5. (5) Verapamil altered the kinetics of recovery from inactivation and the time constant of recovery increased from 197.3 to 502.3 ms (at a membrane potential of about −40 mV).