Effect of 3, 4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-qu inolinone (OPC-8212) on the membrane currents of rabbit sino-atrial node cells.

The effects of 3, 4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- quin olinone ( OPC -8212) (5-30 micrograms/ml) on membrane potential and currents were studied by the voltage clamp technique, using small rabbit sinoatrial node preparations. OPC -8212 induced only slight changes in the action potential configuration. A high dose decreased the amplitude and the duration of the action potential and slightly hyperpolarized the maximum diastolic potential. Sinus rate was decreased, but the change was statistically not significant. The maximum rate of rise of the action potential increased in a dose-dependent manner. In voltage clamp experiments, OPC -8212 increased the slow inward current (Is), but reduced the outward current (Ik) and the inward current activated by hyperpolarization (Ih). The degrees of the inactivation of Is (f infinity) and of the steady-state activation of Ik (p infinity) were unchanged against the voltage axis. These results suggest that the increase in Is caused by OPC -8212 could have been due to the increase in the conductance of Is, and the decrease in Ik, due to the reduction in the conductance of Ik.