hERG1a/1b heteromeric currents exhibit amplified attenuation of inactivation in variant 1 short QT syndrome

MJ Mcpate, H Zhang, JM Cordeiro, CE Dempsey, HJ Witchel, JC Hancox

Research output: Contribution to journalArticle (Academic Journal)peer-review

18 Citations (Scopus)

Abstract

Potassium channels encoded by hERG (human ether-à-go-go-related gene) underlie the cardiac rapid delayed rectifier K+ current (IKr) and hERG utations underpin clinically important epolarization disorders. Virtually all lectrophysiological investigations of hERG mutations have studied exclusively the hERG1a isoform; however, recent evidence indicates that native IKr channels may be comprised of hERG1a together with the hERG1b variant, which has a shorter N-terminus. Here, for the first time, electrophysiological effects were studied of a gain-of-function hERG mutation (N588K; responsible for the ‘SQT1’ variant of the short QT syndrome) on current (IhERG1a/1b) carried by co-expressed hERG1a/1b channels. There were no significant effects of N588K on IhERG1a/1b activation or deactivation, but N588K IhERG1a/1b showed little inactivation up to highly positive voltages (6+80 mV), a more marked effect than seen for hERG1a expressed alone. IhERG1a/1b under action potential voltage-clamp, and the effects on this of the N588K mutation, also showed differences from those previously reported for hERG1a. The amplified attenuation of IhERG inactivation for the N588K mutation reported here indicates that the study of coexpressed hERG1a/1b channels should be considered when investigating clinically relevant hERG channel mutations, even if these reside outside of the N-terminus region.
Translated title of the contributionhERG1a/1b heteromeric currents exhibit amplified attenuation of inactivation in variant 1 short QT syndrome
Original languageEnglish
Pages (from-to)111 - 117
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume386 (1)
DOIs
Publication statusPublished - Aug 2009

Fingerprint Dive into the research topics of 'hERG1a/1b heteromeric currents exhibit amplified attenuation of inactivation in variant 1 short QT syndrome'. Together they form a unique fingerprint.

Cite this