EFFECTS OF NOVEL CLASS III ANTIARRHYTHMIC DRUG RP58866 ON IK1 AND Ito IN GUINEA PIG AND CANINE VENTRICULAR MYOCYTES

AIM: Novel class III antiarrhythmic compounds RP58866 are known to block inward rectifier K⁺ current ( I_K1), and have been used as “specific” probes for the physiologic role of I_K1. However, the specificity is not completely established. The present study was designed to determine the effects of RP58866 on I_K1 and transient outward K⁺ current (I_to) in isolated cardia myocytes. METHODS: The tight seal cell clamp technique was used. RESULTS: RP58866 significantly decreased I_K1 in a concentration dependent manner, with an IC₅₀ of (3. 4±0.8) μmol·L^-1 (x±s) at -100 mV in guinea pig ventricular cells. In canine ventricular myocytes, RP58866 significantly inhibited I_to(decreased by 87%±2.1% at 100μmol·L^-1) with IC₅₀ an of (2.3±0.5) μmol·L^-1. CONCLUSION: Our results suggest that RP58866 inhibits I_K1 and I_to in cardiac myocytes with similar potency and that the compound is not a specific IK1 inhibitor.