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.