Electrophysiologic and voltage clamp analysis of the effects of sotalol on isolated cardiac muscle and Purkinje fibers.

Abstract

The effect of dl-, d- and I-sotalol on electrophysiologic characteristics of guinea-pig papillary muscles, sheep and rabbit Purkinje fibers was studied. Standard electrophysiologic and voltage clamp techniques were used. At concentrations between 10(-6) and 10(-4) M, the main effect of sotalol consisted of prolongation of the action potential duration. In voltage clamp experiments this effect correlated with a substantial reduction of the time-dependent K current activated during the plateau of the action potential and a small reduction of the background K current. At concentrations above 10(-4) M, a secondary shortening of the action potential concomitant with a fall in maximal rate of depolarization was seen. In voltage clamp experiments this effect correlated with a decrease of a slowly inactivating Na current. In the absence of catecholamines d- and I-sotalol exerted identical effects on action potentials and voltage clamp currents.