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Characterization of recombinant hERG K(+) channel inhibition by the active metabolite of amiodarone desethyl-amiodarone.

Zhang, YH, Cheng, H, Alexeenko, VA, Dempsey, CE and Hancox, JC (2010) Characterization of recombinant hERG K(+) channel inhibition by the active metabolite of amiodarone desethyl-amiodarone. J Electrocardiol, 43 (5). pp. 440-448.

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Abstract

UNLABELLED: The aim of this study was to determine the effects of desethyl-amiodarone (DEA), the major metabolite of the class III antiarrhythmic drug amiodarone, on human ether-à-go-go-related gene (hERG) encoded potassium channel current. MATERIALS AND METHODS: Whole-cell patch clamp recordings were made at 37 degrees C of ionic current (I(hERG)) carried by recombinant hERG channels expressed in HEK-293 cells. RESULTS: Desethyl-amiodarone inhibited I(hERG) with a half-maximal inhibitory concentration of approximately 158 nmol/L, compared with approximately 47 nmol/L for amiodarone. The inhibitory action of DEA on I(hERG) was contingent on channel gating, showing significant time and voltage dependence. Desethyl-amiodarone also produced an approximately -9 mV shift in the voltage dependence of activation of I(hERG); however, there was no significant preference for activated over inactivated channels. CONCLUSIONS: Because hERG underlies native cardiac "I(Kr)" channels, hERG/I(Kr) inhibition by DEA as well as amiodarone may contribute to the overall effects of amiodarone administration on cardiac repolarization.

Item Type: Article
Authors :
NameEmailORCID
Zhang, YHUNSPECIFIEDUNSPECIFIED
Cheng, HUNSPECIFIEDUNSPECIFIED
Alexeenko, VAv.alexeenko@surrey.ac.ukUNSPECIFIED
Dempsey, CEUNSPECIFIEDUNSPECIFIED
Hancox, JCUNSPECIFIEDUNSPECIFIED
Date : September 2010
Identification Number : https://doi.org/10.1016/j.jelectrocard.2010.04.007
Uncontrolled Keywords : Amiodarone, Analysis of Variance, Anti-Arrhythmia Agents, Ether-A-Go-Go Potassium Channels, Humans, Patch-Clamp Techniques
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:55
Last Modified : 17 May 2017 09:55
URI: http://epubs.surrey.ac.uk/id/eprint/825670

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