Effects of verapamil on rapid Na channel-dependent action potentials of K+-depolarized ventricular fibers

Abstract

We studied the effects of 1 to 3 micrograms/ml of verapamil on Vmax and plateau duration in guinea-pig papillary muscles depolarized from -90 to -55 mV by increasing extracellular potassium from 5.4 to 20 mM. Under the conditions of our experiments, we found that verapamil did not influence the steady-state or recovery characteristics of Vmax at any of the studied K levels even when Vmax was less than 20 V/sec. Thus in the absence of rapid sodium channel blockade, the value of Vmax cannot be used to identify slow channel-dependent action potentials. Verapamil caused no shortening of plateau or total action potential duration when potassium was less than 7.5 mM. Above this level, verapamil caused progressive shortening of plateau and total action potential duration, due to the increase in potassium and not the associated decrease in resting membrane potential. Increasing extracellular calcium shortened plateau duration at all levels of potassium before verapamil but lengthened plateau duration in the high K, verapamil-treated fibers. These results, which can be explained by known effect of verapamil on the slow outward as well as slow inward currents, provide a mechanism whereby verapamil may increase Vmax of K-depolarized but rapid sodium current-dependent premature action potentials.