Kv1.5 Potassium Channel Inhibitors for the Treatment and Prevention of Atrial Fibrillation

The Kv1.5 channel subunit is the putative molecular correlate of the ultrarapidly activating delayed rectifier potassium current, I Kur, detected in human atrial but not ventricular myocytes. Inhibition of Kv1.5 has been widely recognized as a potential therapeutic strategy for the treatment of atrial fibrillation (AF), a major clinical concern, especially in aging populations. This review centers on recent Kv1.5 drug discovery and development, in the context of action potential prolonging antiarrhythmics for the treatment of AF. Collectively, most novel agents are nonselective for Kv1.5. Preclinical along with very limited clinical efficacy data appear to validate Kv1.5 as an effective target to increase atrial refractoriness and to convert fibrillating atria to sinus rhythm. Functional characterization of Kv1.5-specific structural domains and novel assays can help discover better Kv1.5 drugs. Definite proof of concept for Kv1.5 inhibition as an effective antiarrhythmic strategy awaits agents with greater Kv1.5 selectivity and a more detailed characterization of I Kur in human atria and the consequence of its inhibition.