{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:17:20Z","timestamp":1792005440737,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council of Taiwan","award":["NSTC 110-2314-B-038-126-MY2"],"award-info":[{"award-number":["NSTC 110-2314-B-038-126-MY2"]}]},{"name":"National Science and Technology Council of Taiwan","award":["NSTC 112-2314-B-038-102-"],"award-info":[{"award-number":["NSTC 112-2314-B-038-102-"]}]},{"name":"National Science and Technology Council of Taiwan","award":["111TMUH-MOST-22"],"award-info":[{"award-number":["111TMUH-MOST-22"]}]},{"name":"National Science and Technology Council of Taiwan","award":["4-02-004"],"award-info":[{"award-number":["4-02-004"]}]},{"name":"National Science and Technology Council of Taiwan","award":["4-02-005"],"award-info":[{"award-number":["4-02-005"]}]},{"name":"Taipei Medical University Hospital","award":["NSTC 110-2314-B-038-126-MY2"],"award-info":[{"award-number":["NSTC 110-2314-B-038-126-MY2"]}]},{"name":"Taipei Medical University Hospital","award":["NSTC 112-2314-B-038-102-"],"award-info":[{"award-number":["NSTC 112-2314-B-038-102-"]}]},{"name":"Taipei Medical University Hospital","award":["111TMUH-MOST-22"],"award-info":[{"award-number":["111TMUH-MOST-22"]}]},{"name":"Taipei Medical University Hospital","award":["4-02-004"],"award-info":[{"award-number":["4-02-004"]}]},{"name":"Taipei Medical University Hospital","award":["4-02-005"],"award-info":[{"award-number":["4-02-005"]}]},{"name":"Foundation for the Development of Internal Medicine in Okinawa, Japan","award":["NSTC 110-2314-B-038-126-MY2"],"award-info":[{"award-number":["NSTC 110-2314-B-038-126-MY2"]}]},{"name":"Foundation for the Development of Internal Medicine in Okinawa, Japan","award":["NSTC 112-2314-B-038-102-"],"award-info":[{"award-number":["NSTC 112-2314-B-038-102-"]}]},{"name":"Foundation for the Development of Internal Medicine in Okinawa, Japan","award":["111TMUH-MOST-22"],"award-info":[{"award-number":["111TMUH-MOST-22"]}]},{"name":"Foundation for the Development of Internal Medicine in Okinawa, Japan","award":["4-02-004"],"award-info":[{"award-number":["4-02-004"]}]},{"name":"Foundation for the Development of Internal Medicine in Okinawa, Japan","award":["4-02-005"],"award-info":[{"award-number":["4-02-005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucagon-like peptide-1 (GLP-1) receptor agonists are associated with reduced atrial fibrillation risk, but the mechanisms underlying this association remain unclear. The GLP-1 receptor agonist directly impacts cardiac Ca2+ homeostasis, which is crucial in pulmonary vein (PV, the initiator of atrial fibrillation) arrhythmogenesis. This study investigated the effects of the GLP-1 receptor agonist on PV electrophysiology and Ca2+ homeostasis and elucidated the potential underlying mechanisms. Conventional microelectrodes and whole-cell patch clamp techniques were employed in rabbit PV tissues and single PV cardiomyocytes before and after GLP-1 (7-36) amide, a GLP-1 receptor agonist. Evaluations were conducted both with and without pretreatment with H89 (10 \u03bcM, an inhibitor of protein kinase A, PKA), KN93 (1 \u03bcM, an inhibitor of Ca2+\/calmodulin-dependent protein kinase II, CaMKII), and KB-R7943 (10 \u03bcM, an inhibitor of Na+\/Ca2+ exchanger, NCX). Results showed that GLP-1 (7-36) amide (at concentrations of 1, 10, and 100 nM) reduced PV spontaneous activity in a concentration-dependent manner without affecting sinoatrial node electrical activity. In single-cell experiments, GLP-1 (7-36) amide (at 10 nM) reduced L-type Ca2+ current, NCX current, and late Na+ current in PV cardiomyocytes without altering Na+ current. Additionally, GLP-1 (7-36) amide (at 10 nM) increased sarcoplasmic reticulum Ca2+ content in PV cardiomyocytes. Furthermore, the antiarrhythmic effects of GLP-1 (7-36) amide on PV automaticity were diminished when pretreated with H89, KN93, or KB-R7943. This suggests that the GLP-1 receptor agonist may exert its antiarrhythmic potential by regulating PKA, CaMKII, and NCX activity, as well as modulating intracellular Ca2+ homeostasis, thereby reducing PV arrhythmogenesis.<\/jats:p>","DOI":"10.3390\/ijms241713100","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T07:25:24Z","timestamp":1692775524000},"page":"13100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Glucagon-like Peptide-1 Receptor Activation Reduces Pulmonary Vein Arrhythmogenesis and Regulates Calcium Homeostasis"],"prefix":"10.3390","volume":"24","author":[{"given":"Chao-Shun","family":"Chan","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fong-Jhih","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Chang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Kuo","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-6249","authenticated-orcid":false,"given":"Satoshi","family":"Higa","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa 9012131, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ann","family":"Chen","sequence":"additional","affiliation":[{"name":"Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Clinical Medicine and Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"},{"name":"Cardiovascular Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7224-4491","authenticated-orcid":false,"given":"Yi-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Cardiovascular Research Center, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC","volume":"42","author":"Hindricks","year":"2021","journal-title":"Eur. 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