Amiodarone Inhibits Apamin-Sensitive Potassium Currents

作者：Turker Isik; Yu Chih Chieh; Chang Po Cheng; Chen Zhenhui; Sohma Yoshiro; Lin Shien Fong; Chen Peng Sheng; Ai Tomohiko^*

来源：PLos One, 2013, 8(7): e70450.

DOI：10.1371/journal.pone.0070450

Background: Apamin sensitive potassium current (I-KAS), 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 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 (IC50, 2.67 +/- 0.25 mu M with 1 mu M intrapipette Ca2+). Maximal inhibition was observed with 50 mu M amiodarone which inhibited 85.6 +/- 3.1% of I-KAS induced with 1 mu M intrapipette Ca2+ (n = 3). I-KAS inhibition by amiodarone was not voltage-dependent, but was Ca2+-dependent: 30 mu M amiodarone inhibited 81.5 +/- 1.9% of I-KAS induced with 1 mu M 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 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 Ca2+ concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles.

• 出版日期2013-7-29