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IMR Press / FBS / Volume 14 / Issue 4 / DOI: 10.31083/j.fbs1404031
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Unraveling the Role of K2P Channels in Atrial Fibrillation
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1 Department of Medicine, Stanford Cardiovascular Institute, Stanford, CA 94304, USA
*Correspondence: gemondej@stanford.edu (Gema Mondéjar-Parreño)
Front. Biosci. (Schol Ed) 2022, 14(4), 31; https://doi.org/10.31083/j.fbs1404031
Submitted: 30 July 2022 | Revised: 29 September 2022 | Accepted: 8 October 2022 | Published: 22 November 2022
This is an open access article under the CC BY 4.0 license.
Abstract

Atrial fibrillation (AF) is a condition in which the electrical signals in the upper heart chambers (atria) are rapid and disorganized, producing an irregular and chaotical heartbeat. The sinus rhythm should be between 60 to 100 bpm at rest, while the heart rhythm in AF patients may be over 140 bpm. Either structural and electro-mechanical remodeling of the atrial tissue underlies the perpetuation and evolution of AF from the paroxysmal to persistent form. Unravelling the different pathological pathways involved in AF that lead to arrhythmogenesis and atrial remodeling is needed to discovery new and effective therapeutic approaches. A variety of drugs are available to convert and maintain the AF patient in a normal sinus rhythm; however, these strategies have limited chances of success or fail with the progression of AF to more persistent/permanent forms. Consequently, it is necessary to find new therapeutic targets for the relief of persistent or chronic AF forms, as well as the development of new and more effective pharmacological tools. The atrial specific two-pore domain K${}^{+}$ channels (K${}_{2}$P) constitute the background K${}^{+}$ current on atrial cardiomyocytes and modulate cell excitability emerging as novel targets in this disease and avoiding ventricle side effects. Moreover, several antiarrhythmic drugs used in AF treatment exert their mechanism of action in part by modulation of K${}_{2}$P channels. Thus far, TWIK-1, TREK-1, TASK-1, TASK-2 and TASK-3 channel have been identified as responsible for background currents I${}_{\text{K2P}}$ current in atrial cells; however, it is not excluded that other K${}_{2}$P${}_{\text{X}}$ subunits or subfamilies have physiological roles in atria. To date, a great diversity openers, activators and blockers of K${}_{2}$P channel have been identified, particularly those targeting TASK and TREK channels. Several studies have demonstrated that the expression of TWIK-1, TREK-1, TASK-1, TASK-2 and TASK-3 are dysregulated in AF and their pharmacology rescue could suppose a novel therapy in AF. The main objective is to examine the regulation of K${}_{2}$P channels and the current K${}_{2}$P channels pharmacological modulators for AF treatment.

Keywords
atrial fibrillation
two pore domain K+ channels
electrophysiological remodeling
pharmacology
Funding
#872244/American Heart Association (AHA) Postdoc Award
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