Mechanism of Proarrhythmic Effects of Potassium Channel Blockers

Prolongation of the cardiac action potential by K channel blockers is well recognized as an antiarrhythmic mechanism, but can exacerbate to life-threatening arrhythmia. The risk for drug-induced torsades de pointes arrhythmia and subsequent ventricular fibrillation is best documented for Kv11.1 (hERG) and Kv7.1 (KvLQT1) channel blockers. Potassium channels with predominant expression in the atrial myocardium may be beneficial in supraventricular arrhythmias without proarrhythmic risk in the ventricles. Many compounds target K channels that were only recently discovered to also be expressed in the heart (eg, K2P and SK channels). The antiarrhythmic and proarrhythmic potential of such compounds is discussed.