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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 (US)
Article numbere70450
JournalPLoS ONE
Volume8
Issue number7
DOIs
StatePublished - Jul 29 2013

Fingerprint

Apamin
Amiodarone
Potassium
potassium
calcium
kidney cells
Electric potential
patch-clamp technique
Kidney
potassium channels
action potentials
Potassium Channels
Clamping devices
shortenings
Patch-Clamp Techniques
Ventricular Fibrillation
Metabolites
inhibitory concentration 50
Action Potentials
Inhibitory Concentration 50

ASJC Scopus subject areas

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

Cite this

Amiodarone Inhibits Apamin-Sensitive Potassium Currents. / Turker, Isik; Yu, Chih Chieh; Chang, Po Cheng; Chen, Zhenhui; Sohma, Yoshiro; Lin, Shien Fong; Chen, Peng Sheng; Ai, Tomohiko.

In: PLoS ONE, Vol. 8, No. 7, e70450, 29.07.2013.

Research output: Contribution to journalArticle

Turker, Isik ; Yu, Chih Chieh ; Chang, Po Cheng ; Chen, Zhenhui ; Sohma, Yoshiro ; Lin, Shien Fong ; Chen, Peng Sheng ; Ai, Tomohiko. / Amiodarone Inhibits Apamin-Sensitive Potassium Currents. In: PLoS ONE. 2013 ; Vol. 8, No. 7.
@article{9ba82a26f499444ab78afcaaa2f75310,
title = "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.",
author = "Isik Turker and Yu, {Chih Chieh} and Chang, {Po Cheng} and Zhenhui Chen and Yoshiro Sohma and Lin, {Shien Fong} and Chen, {Peng Sheng} and Tomohiko Ai",
year = "2013",
month = "7",
day = "29",
doi = "10.1371/journal.pone.0070450",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Amiodarone Inhibits Apamin-Sensitive Potassium Currents

AU - Turker, Isik

AU - Yu, Chih Chieh

AU - Chang, Po Cheng

AU - Chen, Zhenhui

AU - Sohma, Yoshiro

AU - Lin, Shien Fong

AU - Chen, Peng Sheng

AU - Ai, Tomohiko

PY - 2013/7/29

Y1 - 2013/7/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84880842358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880842358&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0070450

DO - 10.1371/journal.pone.0070450

M3 - Article

C2 - 23922993

AN - SCOPUS:84880842358

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e70450

ER -