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

Abstract Effective and safe pharmacological management of cardiac arrhythmia still constitutes a major clinical challenge. Outward potassium currents mediated by two-pore-domain potassium (K 2P ) channels promote repolarization of excitable cells. In the heart, inhibition or genetic inactivation of K 2P currents results in action potential prolongation. Human K 2P 3.1 (TASK-1) channels are predominantly expressed in the atria and represent targets for the treatment of atrial fibrillation. In addition, stretch-sensitive K 2P 2.1 (TREK-1) channels are implicated in mechanoelectrical feedback and arrhythmogenesis in atrial and ventricular tissue. K 2P 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 K 2P channels. Therapeutic implications with emphasis on atrial fibrillation are highlighted.