Inhibition of cardiac two-pore-domain K+ (K2P) channels – an emerging antiarrhythmic concept

Effective and safe pharmacological management of cardiac arrhythmia still constitutes a major clinical challenge. Outward potassium currents mediated by two-pore-domain potassium (K2P) channels promote repolarization of excitable cells. In the heart, inhibition or genetic inactivation of K2P currents results in action potential prolongation. Human K2P3.1 (TASK-1) channels are predominantly expressed in the atria and represent targets for the treatment of atrial fibrillation. In addition, stretch-sensitive K2P2.1 (TREK-1) channels are implicated in mechanoelectrical feedback and arrhythmogenesis in atrial and ventricular tissue. K2P current inhibition by clinically used antiarrhythmic drugs indicates a role of the channels as potential drug targets. This work summarizes the current knowledge on function, pharmacology, and significance of cardiac K2P channels. Therapeutic implications with emphasis on atrial fibrillation are highlighted.