Effect of OPC-8490 on the membrane potentials and membrane currents of single guinea-pig myocytes.
The direct actions of OPC-8490 on mammalian myocardium were examined by determination of the drug's effects on the action potentials of isolated guinea-pig single ventricular cells and on the underlying ionic currents. OPC-8490 (10(-6) to 10(-4) M) did not alter the resting membrane potential, but rather produced a dose-dependent prolongation of the duration of the action potential. The amplitude of the action-potential plateau was also increased by OPC-8490. Whole-cell voltage clamp experiments revealed that OPC-8490 blocks myocardial delayed outward K+ current (IK), which regulates repolarization of the action potentials. However Ik1, which regulates the resting membrane potential, was not changed by OPC-8490. Ca current (ICa) was increased by OPC-8490 in a dose-dependent and reversible manner. These results suggest that OPC-8490 augments the plateau amplitude and increases the duration of the action potentials by not only increasing ICa, but also by decreasing delayed outward K+ currents. Moreover, OPC-8490 did not affect the intracellular concentration of cyclic AMP in single cells. The OPC-8490 increase in ICa was thus unlikely to be mediated by a process involving cyclic AMP.
Momose
Y
Y
Department of Pharmacology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Sasayama
S
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D011863:Radioimmunoassay; D016276:Ventricular Function
D002316:Cardiotonic Agents; D010879:Piperazines; D015363:Quinolones; C061380:OPC 8490; D000242:Cyclic AMP