Membrane current changes responsible for the positive inotropic effect of OPC-8212, a new positive inotropic agent, in single ventricular cells of the guinea pig heart.

Effects of OPC-8212, a new positive inotropic drug, and 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, on membrane currents were examined in single ventricular cells of the guinea pig heart. Single ventricular cells were prepared by the collagenase dispersion procedure. Both OPC-8212 (0.1 mM) and IBMX (0.1 mM) augmented the plateau and increased the duration of the action potential without affecting the resting membrane potential. Under voltage clamp condition, OPC-8212 (0.1 mM) increased the inward calcium current and decreased the delayed outward and the inward-rectifying potassium current. IBMX (0.1 mM) increased not only the inward calcium but also the delayed outward current. The isolated inward calcium current obtained by intra- and extracellular perfusion with Cs+, was increased by both drugs. When the inward calcium current was abolished by superfusion with D600 (10 microM) or Co++ (0.9 mM), OPC-8212 (0.1 mM) decreased the delayed outward and the inward-rectifying potassium current. On the other hand, IBMX (0.1 mM) increased the delayed outward current. From these results it can be concluded that OPC-8212 augments the plateau and increases duration of the action potential not only by increasing the inward calcium but also by decreasing both the delayed outward and the inward-rectifying potassium current, and the effects can be a cause of the positive inotropic effect of this drug.