Voltage-dependent inhibition of the delayed outward potassium current by OPC-8490, a novel positive inotropic agent, in isolated atrial myocytes of guinea-pig heart

Abstract

To elucidate the ionic mechanisms underlying prolongation of the action potential by OPC-8490, a novel positive inotropic agent, we examined effects of the drug on the membrane currents in isolated atrial myocytes of guinea-pig heart. The tight-seal whole cell clamp technique was used. In the current clamp condition, OPC-8490 prolonged the atrial action potential in a concentration-dependent fashion. In the voltage clamp condition, OPC-8490 affected neither the conventional L type Ca current nor the outward IK1 current significantly. The drug blocked the delayed outward K current (IK) in a concentration-dependent fashion. At a constant concentration of the drug, inhibition of IK became more marked as the membrane potential became more negative. The tail current of IK could be fitted by a sum of two exponentials (fast and slow components). OPC-8490 blocked the fast component more prominently than the slow one. Time constants of both components were not affected significantly by the drug. In conclusion, OPC-8490 prolongs the cardiac action potential mainly by blocking IK in a voltage-dependent and time-dependent fashion.