Channelpedia

In vivo gene transfer of Kv1.5 normalizes action potential duration and shortens QT interval in mice with long QT phenotype.


Authors: Michael Brunner, Sodikdjon A Kodirov, Gary F Mitchell, Peter D Buckett, Katsushi Shibata, Eduardo J Folco, Linda Baker, Guy Salama, Danny P Chan, Jun Zhou, Gideon Koren

Journal, date & volume: Am. J. Physiol. Heart Circ. Physiol., 2003 Jul , 285, H194-203

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12793978

Channelpedia reference in: Kv1.5

Abstract
Mutations in cardiac voltage-gated K+ channels cause long QT syndrome (LQTS) and sudden death. We created a transgenic mouse with a long QT phenotype (Kv1DN) by overexpression of a truncated K+ channel in the heart and investigated whether the dominant negative effect of the transgene would be overcome by the direct injection of adenoviral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the myocardium. End points at 3-10 days included electrophysiology in isolated cardiomyocytes, surface ECG, programmed stimulation of the right ventricle, and in vivo optical mapping of action potentials and repolarization gradients in Langendorff-perfused hearts. Overexpression of Kv1.5 reconstituted a 4-aminopyridine-sensitive outward K+ current, shortened the action potential duration, eliminated early afterdepolarizations, shortened the QT interval, decreased dispersion of repolarization, and increased the heart rate. Each of these changes is consistent with a physiologically significant primary effect of adenoviral expression of Kv1.5 on ventricular repolarization of Kv1DN mice.