Referenced in: none

Automatically associated channels: Kv11.1 , Slo1

Title: Expression of human ERG K+ channels in the mouse heart exerts anti-arrhythmic activity.

Authors: Anne Royer, Sophie Demolombe, Aziza El Harchi, Khaï Le Quang, Julien Piron, Gilles Toumaniantz, David Mazurais, Chloé Bellocq, Gilles Lande, Cecile Terrenoire, Howard K Motoike, Jean-Christophe Chevallier, Gildas Loussouarn, Colleen E Clancy, Denis Escande, Flavien Charpentier

Journal, date & volume: Cardiovasc. Res., 2005 Jan 1 , 65, 128-37

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15621040

Abstract
The K(+) channel encoded by the human ether-a-go-go-related gene (HERG) is crucial for repolarization in the human heart. In order to investigate the impact of HERG current (I(Kr)) on the incidence of cardiac arrhythmias, we generated a transgenic mouse expressing HERG specifically in the heart.ECG recordings at baseline showed no obvious difference between transgenic and wild-type (WT) mice with the exception of the T wave, which was more negative in transgenic mice than in WT mice. E4031 (20 mg/kg) prolonged the QTc interval and flattened the T wave in transgenic mice, but not in WT mice. Injection of BaCl(2) (25 mg/kg) induced short runs of ventricular tachycardia in 9/10 WT mice, but not in transgenic animals. Atrial pacing reproducibly induced atrial tachyarrhythmias in 11/15 WT mice. In contrast, atrial arrhythmia was inducible in only 2/11 transgenic mice. When pretreated with dofetilide (10 mg/kg), transgenic mice were as sensitive to experimental arrhythmias as WT mice. Microelectrode studies showed that atrial action potentials have a steeper slope of duration-rate adaptation in WT than in transgenic mice. Transgenic mice were also characterized by a post-repolarization refractoriness, which could result from the substantial amount of I(Kr) subsisting after repolarization as assessed with action potential-clamp experiments and simulations with a model of the transgenic mouse action potential.HERG expression in the mouse heart can protect against experimental induction of arrhythmias. This is the first report of such a protective effect of HERG in vivo.