THE NOVEL CLASS-III ANTIARRHYTHMICS NE-10064 AND NE-10133 INHIBIT I-SK CHANNELS EXPRESSED IN XENOPUS-OOCYTES AND I-KS IN GUINEA-PIG CARDIAC MYOCYTES

Slowly activating, voltage-dependent I-sK channels were expressed in Xenopus oocytes after injection of rat I-sK protein cRNA and recorded with the two-microelectrode voltage-clamp technique. The I-sK currents were inhibited by the new class III antiarrhythmic drugs NE-10064 and NE-10133. These compounds were equally potent in inhibiting a slowly activating potassium current (I-Ks) in guinea pig ventricular myocytes. No effects of these compounds could be observed on several other cloned delayed rectifier potassium channels, nor did they affect the inward rectifier current, I-K1, in guinea pig cardiac myocytes at the concentrations tested. The blockade of I-sK channels may contribute to the class III antiarrhythmic efficacy of these novel antiarrhythmics. (C) 1994 Academic Press, Inc.