Atrial fibrillation: is NO an answer for refractoriness?

The progressive nature of atrial fibrillation (AF) has been attributed to alteration in the electrophysiological properties of the atrial myocardium. As a net effect, a shortening in the refractory period contributes to the substrate, allowing ectopic complex arising and re-entry [1]. Transmembrane ion channel activity determines atrial action potential (AP) shape. Whereas Na and Ca channels are responsible for depolarizing currents, K channels are responsible for repolarizing currents and therefore shortening of the AP duration. The refractory period is directly correlated to the AP duration. Class III antiarrhythmic drugs are predicted to lengthen AP duration and to prevent subsequent AF. In human atrium, three components contribute to the late repolarizing K current: an ‘ultra-rapid’ component (IKur), a ‘rapid’ component (IKr), and a ‘slow’ component (IKs), referring to their voltage-dependent activation kinetics. Among the genes encoding the proteins underlying these currents, HERG codes for the K channel generating IKr, the target of class III antiarrhythmic drugs. Since this gene is also expressed at the ventricular level, pharmacological intervention on IKr may be responsible for ventricular AP lengthening and potentially for ventricular arrhythmias. Inversely, IKur is specific to the atrium in humans and is carried by Kv1.5 channels [2,3]. Kv1.5 appears to be an appealing and specific target for pharmacological treatment of atrial tachyarrhythmias. Indeed, recent in vivo studies of Kv1.5 blockers in animal models support the antiarrhythmic efficacy of this approach [4–6]. However, considering Kv1.5 as a potential target for AF management may be questioned. Indeed, the Kv1.5-related