In Phase III (the rapid repolarization phase) of the cardiac action potential, two potassium currents, I_Ks and I_Kr, provide the principal repolarizing currents in cardiac myocytes for the termination of action potentials. Antiarrhythmic drugs are a class of cardiovascular drugs that affect the cardiac action potential to suppress abnormal rhythms of the heart (cardiac arrhythmias) such as atrial fibrillation, atrial flutter, ventricular tachycardia and ventricular fibrillation (Thomas et al. 2006, Hassan et al. 2013). In the Vaughan Williams classification of cardiovascular drugs ((Williams 1975), class III agents interfere with potassium (K+) channels, predominantly blocking them and thereby prolonging repolarization. Class III agents do not affect the sodium channel therefore conduction velocity is not decreased. Prolongation of the action potential duration and refractory period, together with a normal conduction velocity, prevents re-entrant arrhythmias.

Class III agents that affect the I_Kr current bind to and block potassium voltage-gated channel subfamily H member1 (KCNH2, aka ether-a-go-go-related protein 1, HERG, Kv11.1). These agents include dofetilide, ibutilide and E-4031. Dofetilide is used for the maintenance of sinus rhythm in individuals prone to the occurrence of atrial fibrillation and flutter arrhythmias (Gomez-Varela et al. 2006). Like other antiarrhythmic agents in its class, torsades de pointes (a specific type of abnormal heart rhythm that can lead to sudden cardiac death) may be induced as a consequence of therapy (Roukoz & Saliba 2007). Ibutilide is indicated for cardioconversion of atrial fibrillation and atrial flutter to normal sinus rhythm (Perry et al. 2004, Doggrell & Hancox 2005). E-4031 is an experimental class III antiarrhythmic drug that blocks KCNH2 K+ channels, thereby mediating the I_Kr current, which repolarizes myocardial cells (Katritsis et al. 1997).