Channelpedia

Ultra-rapid delayed rectifier channels - molecular basis and therapeutic implications.


Authors: Ursula Ravens, Erich Wettwer

Journal, date & volume: , 2010 Dec 15 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21159668

Channelpedia reference in: Kv1.5

Abstract
The ultrarapid delayed rectifier channels have attracted considerable interest as targets for "atrial-selective" antiarrhythmic drugs because they contribute to atrial but not to ventricular repolarization. Thus I(Kur) channel blockers are expected to prolong selectively atrial effective refractory period without inducing proarrhythmic effects due to excessive ventricular action potential prolongation. Here we provide an overview of the properties of I(Kur) channels in expression systems and native cardiomyocytes. The ion conducting pore of the channel is formed by 4 Kv1.5 α-subunits, whereas the ancillary β-subunits Kvβ1.2, Kvβ1.3 and Kvβ2.1 control channel trafficking and plasmamembrane integration as well as activation and inactivation kinetics. Investigation of I(Kur) channel blockers in cardiomyocytes is complicated by (i) substantial overlap of I(Kur) with other currents notably transient outward current I(to) (ii) by lack of drug selectivity, and (iii) by disease-induced regulation of I(Kur). Some new compounds developed as I(Kur) blockers are described and their efficacy in treatment of atrial fibrillation is discussed. Current evidence suggests that pure I(Kur) channel block may not be sufficient to suppress atrial fibrillation.