Iijima T, Taira N
J Pharmacol Exp Ther. 1987 Feb;240(2):657-62.
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.
研究了新型正性肌力药物OPC - 8212和磷酸二酯酶抑制剂3 - 异丁基 - 1 - 甲基黄嘌呤（IBMX）对豚鼠心脏单个心室肌细胞膜电流的影响。采用胶原酶分散法制备单个心室肌细胞。OPC - 8212（0.1 mM）和IBMX（0.1 mM）均可增强动作电位的平台期并延长动作电位持续时间，而不影响静息膜电位。在电压钳制条件下，OPC - 8212（0.1 mM）增加内向钙电流，降低延迟外向钾电流和内向整流钾电流。IBMX（0.1 mM）不仅增加内向钙电流，还增加延迟外向电流。通过细胞内和细胞外灌注Cs + 分离得到的内向钙电流，两种药物均可使其增加。当用D600（10 microM）或Co ++（0.9 mM）灌流消除内向钙电流时，OPC - 8212（0.1 mM）降低延迟外向钾电流和内向整流钾电流。另一方面，IBMX（0.1 mM）增加延迟外向电流。从这些结果可以得出结论，OPC - 8212增强动作电位的平台期并延长其持续时间，不仅是通过增加内向钙电流，还通过降低延迟外向钾电流和内向整流钾电流，这些作用可能是该药物正性肌力作用的原因。
