Effects of Verapamil and Its Optical Isomers on Repetitive Slow Responses Induced by Electrical Depolarization in Canine Ventricular Myocardium

Abstract

The electrophysiological effects of verapamil (racemic compounds) and its optical (d- and l-) isomers on canine ventricular myocardial fibers were investigated in current clamp conditions using single sucrose gap chamber and microelectrodes. The current-voltage (I-V) relationships were obtained in normal and low Na (12 mM)-low Ca (0.45 mM) solutions with and without the drugs. Verapamil and its optical isomers blocked repetitive action potential discharges (slow responses) induced by depolarizing DC-currents but l-isomer was more potent than d-isomer in suppressing these responses. The difference in the potency was attributed to their different actions on the steady state I-V relationships: l-isomer increased time independent membrane conductance to K ions while d-isomer did not. This effect of l-isomer may favor the suppression of phase 4 depolarization and reduce the frequency of repetitive action potential discharges in depolarized ventricular muscle more effectively than d-isomer.