{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:27:05Z","timestamp":1788956825244,"version":"build-2803163510"},"reference-count":85,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>This manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (KACh) channels in the pathogenesis of atrial fibrillation (AF), a common cardiac arrhythmia. It delves into the molecular and cellular mechanisms that underpin AF, emphasizing the vital function of KACh channels in modulating the atrial action potential and facilitating arrhythmogenic conditions. This study underscores the dual nature of KACh activation and its genetic regulation, revealing that specific variations in potassium channel genes, such as Kir3.4 and K2P3.1, significantly influence the electrophysiological remodeling associated with AF. Furthermore, this manuscript identifies the crucial role of the KACh-mediated current, IKACh, in sustaining arrhythmia through facilitating shorter re-entry circuits and stabilizing the re-entrant circuits, particularly in response to vagal nerve stimulation. Experimental findings from animal models, which could not induce AF in the absence of muscarinic activation, highlight the dependency of AF induction on KACh channel activity. This is complemented by discussions on therapeutic interventions, where KACh channel blockers have shown promise in AF management. Additionally, this study discusses the broader implications of KACh channel behavior, including its ubiquitous presence across different cardiac regions and species, contributing to a comprehensive understanding of AF dynamics. The implications of these findings are profound, suggesting that targeting KACh channels might offer new therapeutic avenues for AF treatment, particularly in cases resistant to conventional approaches. By integrating genetic, cellular, and pharmacological perspectives, this manuscript offers a holistic view of the potential mechanisms and therapeutic targets in AF, making a significant contribution to the field of cardiac arrhythmia research.<\/jats:p>","DOI":"10.3390\/cells13121014","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T08:49:03Z","timestamp":1718009343000},"page":"1014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Role of KACh Channels in Atrial Fibrillation"],"prefix":"10.3390","volume":"13","author":[{"given":"Vadim","family":"Mitrokhin","sequence":"first","affiliation":[{"name":"Institute of Physiology, Federal State Autonomous Educational Institution of Higher Education \u201cN.I. Pirogov, Russian National Research Medical University\u201d Ministry of Health, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4498-7359","authenticated-orcid":false,"given":"Nikola","family":"Hadzi-Petrushev","sequence":"additional","affiliation":[{"name":"Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Kazanski","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Federal State Autonomous Educational Institution of Higher Education \u201cN.I. 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Pirogov, Russian National Research Medical University\u201d Ministry of Health, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasija","family":"Rodina","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Federal State Autonomous Educational Institution of Higher Education \u201cN.I. Pirogov, Russian National Research Medical University\u201d Ministry of Health, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Zolotareva","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Federal State Autonomous Educational Institution of Higher Education \u201cN.I. 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Cyril and Methodius University, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mariani, M.V., Pierucci, N., Trivigno, S., Cipollone, P., Piro, A., Chimenti, C., Rocca, D.G.D., Miraldi, F., Vizza, C.D., and Lavalle, C. (2024). Probability Score to Predict Spontaneous Conversion to Sinus Rhythm in Patients with Symptomatic Atrial Fibrillation When Less Could Be More. J. Clin. Med., 13.","DOI":"10.3390\/jcm13051470"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1161\/CIRCEP.107.754564","article-title":"Atrial remodeling and atrial fibrillation: Mechanisms and implications","volume":"1","author":"Nattel","year":"2008","journal-title":"Circ. Arrhythm. 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