Amiodarone Inhibits Apamin-Sensitive Potassium Currents

Abstract

Background:Apamin sensitive potassium current (IKAS), carried by the type 2 small conductance Ca2+-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.Objective:To test the hypothesis that amiodarone inhibits IKAS in human embryonic kidney 293 (HEK-293) cells.Methods:We used the patch-clamp technique to study IKAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.Results:Amiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67±0.25 μM with 1 μM intrapipette Ca2+). Maximal inhibition was observed with 50 μM amiodarone which inhibited 85.6±3.1% of IKAS induced with 1 μM intrapipette Ca2+ (n = 3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca2+-dependent: 30 μM amiodarone inhibited 81.5±1.9% of IKAS induced with 1 μM Ca2+ (n = 4), and 16.4±4.9% with 250 nM Ca2+ (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca2+ dependent inhibition of IKAS.Conclusion:Both amiodarone and desethylamiodarone inhibit IKAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca2+ concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles. © 2013 Turker et al.