Open AccessAmiodarone Inhibits Apamin-Sensitive Potassium Currents
Author(s) -
Isik Turker,
Chih Chieh Yu,
Po Cheng Chang,
Zhenhui Chen,
Yoshiro Saito,
Shien Fong Lin,
Peng Sheng Chen,
Tomohiko Ai
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0070450
Subject(s) - apamin , amiodarone , pharmacology , medicine , chemistry , endocrinology , potassium channel , patch clamp , electrophysiology , atrial fibrillation
Background Apamin sensitive potassium current ( I KAS ), carried by the type 2 small conductance Ca 2+ -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 I KAS in human embryonic kidney 293 (HEK-293) cells. Methods We used the patch-clamp technique to study I KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration. Results Amiodarone inhibited I KAS in a dose-dependent manner (IC 50 , 2.67±0.25 µM with 1 µM intrapipette Ca 2+ ). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6±3.1% of I KAS induced with 1 µM intrapipette Ca 2+ (n = 3). I KAS inhibition by amiodarone was not voltage-dependent, but was Ca 2+ -dependent: 30 µM amiodarone inhibited 81.5±1.9% of I KAS induced with 1 µM Ca 2+ (n = 4), and 16.4±4.9% with 250 nM Ca 2+ (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca 2+ dependent inhibition of I KAS . Conclusion Both amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca 2+ concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles.