[Effects of bupivacaine on Na+ and Ca2+ currents in single canine ventricular cells]

The effects of bupivacaine on Na+ and Ca2+ currents in single canine isolated left ventricular cells were examined using whole-cell voltage clamp technique to reveal the mechanism of its negative inotropism. The cells were isolated by enzymatic dispersion and superfused in an oxygenated Tyrode's solution. Bupivacaine 10(-6) M decreased the amplitude of INa and delayed the peak time. These effects were dose and frequency dependent. At a concentration of 10(-3) M, bupivacaine abolished INa. Meanwhile, bupivacaine did not modify ICa at a concentration of 10(-6) M. At 10(-5) M bupivacaine, the amplitude of ICa was depressed by 22% and the depression was dose dependent. These results suggest that low concentration (10(-6) M) of bupivacaine depresses contraction, by reducing intracellular Ca2+ secondary to reduction in intracellular Na+ activity and the Na+-Ca2+ exchange mechanism. At higher concentrations, the reduction in contraction caused by bupivacaine may result partly from a reduced influx of Ca2+.