Class III (KCNA5) antiarrhythmics bind KCNA5 tetramers

Stable Identifier
Reaction [binding]
Homo sapiens
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The potassium voltage-gated channel subfamily A member 5 (KCNA5, Kv1.5) mediates the ultra-rapidly activating delayed rectifier outward K+ current (IKur) in cardiac tissue, specifically the atria. This current plays a central role in atrial cell repolarization. Modulators of the atrial-selective IKur current (via blockade of KCNA5) could prove to be novel therapeutic approaches to treat atrial fibrillation (AF) since KCNA5 channels do not conduct IKur currents in ventricles (Tamcun et al. 19991). Class III antiarrhythmics that block KCNA5 include amiodarone and dronedarone. Amiodarone is an antiarrhythmic drug used to treat various tachycardias, as well as ventricular (VF) and atrial fibrillation (AF) (Kowey et al. 1995). It has electrophysiological properties of all the antiarrhythmic classes (Kodama et al. 1997). Dronedarone is primarily a class III anti-arrhythmic agent but it has electrophysiological properties of all antiarrhythmic classes. Using whole-cell patch-clamp techniques applied to human atrial myocytes, dronedarone inhibited transmembrane potassium currents: ultrarapid-delayed rectifier (IKur), delayed rectifier (IKs and IKr), transient outward (Ito), and inward rectifier (IK1) (Wegener et al. 2006, Salem et al. 2010).
Literature References
PubMed ID Title Journal Year
27147833 Dronedarone in the management of atrial fibrillation

Chetty, CM, Bharani, K, Saleem, TsM, Gauthaman, K

Open Access Emerg Med 2010
7586312 Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. The Intravenous Amiodarone Multicenter Investigators Group

Lindsay, BD, Pacifico, A, Herre, JM, Levine, JH, Kopelman, HA, Plumb, VJ, Janosik, DL, Kowey, PR, Scheinman, MM

Circulation 1995
16939434 Dronedarone: an emerging agent with rhythm- and rate-controlling effects

Ehrlich, JR, Hohnloser, SH, Wegener, FT

J. Cardiovasc. Electrophysiol. 2006
Orthologous Events
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