Referenced in: none

Automatically associated channels: Kv11.1

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

Authors: Yi H Zhang, Hongwei Cheng, Vadim A Alexeenko, Christopher E Dempsey, Jules C Hancox

Journal, date & volume: J Electrocardiol, 2010 Sep-Oct , 43, 440-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20493497

Abstract
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.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.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.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.