We studied the effects of bupivacaine on the contractility and membrane potentials in isolated dog papillary muscle. Bupivacaine (10(-6)-10(-4) M) produced dose-dependent depression of twitch tension elicited by electrical stimulation. These inhibitory effects were greater at high frequencies of stimulation (2, 3 Hz) than at low frequencies (less than 1 Hz). Bupivacaine did not alter the resting membrane potential, but produced a reduction in Vmax of the action potentials, in a dose-dependent and reversible manner (concentrations from 10(-6) to 10(-4) M). Bupivacaine 10(-4) M often blocked the fast action potentials in normal Tyrode's solution. In high K+ (26 mM) Tyrode's solution, bupivacaine inhibited both slow action potentials and associated contractions in the presence of isoproterenol. These results suggest that low concentrations of bupivacaine decreases the contraction mainly due to Na+ channel block, whereas at higher concentration, this anesthetic may block Ca2+ channels. In addition, isoproterenol may be clinically effective in the treatment of bupivacaine cardiotoxicity due to stimulation of Ca2+ mediated slow action potentials through beta-receptors.