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.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D011188:Potassium / Q000502:physiology; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*
D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone; D011188:Potassium; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine