title: 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 (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.
authors.affiliation: Department of Cardiology, Medical University Hospital, Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Cardiology, Medical University Hospital, Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Wiedmann
authors.affiliation: Department of Cardiology, Medical University Hospital, Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Schweizer
authors.affiliation: Department of Cardiology, Medical University Hospital, Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, Medical University Hospital, Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. Electronic address: Dierk.Thomas@med.uni-heidelberg.de.
authors.forename: Dierk
authors.initials: D
authors.lastname: Thomas
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D024683:Potassium Channels, Tandem Pore Domain
keywords: Action potential; Antiarrhythmic drug; Atrial fibrillation; Cardiac arrhythmia; K(2P) channel