Amiodarone Inhibits Apamin-Sensitive Potassium Currents

Isik Turker, Chih Chieh Yu, Po Cheng Chang, Zhenhui Chen, Yoshiro Sohma, Shien Fong Lin, Peng Sheng Chen, Tomohiko Ai

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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.

Original languageEnglish
Article numbere70450
JournalPloS one
Volume8
Issue number7
DOIs
Publication statusPublished - 2013 Jul 29

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Turker, I., Yu, C. C., Chang, P. C., Chen, Z., Sohma, Y., Lin, S. F., Chen, P. S., & Ai, T. (2013). Amiodarone Inhibits Apamin-Sensitive Potassium Currents. PloS one, 8(7), [e70450]. https://doi.org/10.1371/journal.pone.0070450