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.
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.
2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Y
Y
Kurachi
Y
Y
Asano
H
H
Ito
T
T
Sugimoto
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D015363:Quinolones / Q000494:pharmacology*
D015220:Calcium Channels; D007473:Ion Channels; D010879:Piperazines; D015221:Potassium Channels; D015363:Quinolones; C061380:OPC 8490