title: Therapeutic targeting of two-pore-domain potassium (K(2P)) channels in the cardiovascular system.
abstract: The improvement of treatment strategies in cardiovascular medicine is an ongoing process that requires constant optimization. The ability of a therapeutic intervention to prevent cardiovascular pathology largely depends on its capacity to suppress the underlying mechanisms. Attenuation or reversal of disease-specific pathways has emerged as a promising paradigm, providing a mechanistic rationale for patient-tailored therapy. Two-pore-domain K(+) (K(2P)) channels conduct outward K(+) currents that stabilize the resting membrane potential and facilitate action potential repolarization. K(2P) expression in the cardiovascular system and polymodal K2P current regulation suggest functional significance and potential therapeutic roles of the channels. Recent work has focused primarily on K(2P)1.1 [tandem of pore domains in a weak inwardly rectifying K(+) channel (TWIK)-1], K(2P)2.1 [TWIK-related K(+) channel (TREK)-1], and K(2P)3.1 [TWIK-related acid-sensitive K(+) channel (TASK)-1] channels and their role in heart and vessels. K(2P) currents have been implicated in atrial and ventricular arrhythmogenesis and in setting the vascular tone. Furthermore, the association of genetic alterations in K(2P)3.1 channels with atrial fibrillation, cardiac conduction disorders and pulmonary arterial hypertension demonstrates the relevance of the channels in cardiovascular disease. The function, regulation and clinical significance of cardiovascular K(2P) channels are summarized in the present review, and therapeutic options are emphasized.
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Wiedmann
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lugenbiel
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Staudacher
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Rahm
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Seyler
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Schweizer
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany dierk.thomas@med.uni-heidelberg.de.
authors.forename: Dierk
authors.initials: D
authors.lastname: Thomas
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*
chemical_list: D000889:Anti-Arrhythmia Agents; D024683:Potassium Channels, Tandem Pore Domain
keywords: K2P channel; TWIK-related acid-sensitive K+ channel 1 (TASK-1); anti-arrhythmic therapy; arrhythmia; atrial fibrillation; ion channel