{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T23:42:17Z","timestamp":1771544537455,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Background<\/jats:title>\n Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been reported to improve cardiovascular outcomes, potentially through glucose metabolism-independent mechanisms. However, their mechanism of heart rhythm remains controversial.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We investigated the role of the GABA\n B<\/jats:sub>\n receptor (GABA\n B<\/jats:sub>\n R) in mediating GLP-1RA\u2019s chronotropic and anti-arrhythmic effects in a murine myocardial infarction (MI) model. MI was induced by left anterior descending artery ligation. Cardiomyocyte-specific\n Gabbr1<\/jats:italic>\n -knockout (\n Gabbr1<\/jats:italic>\n cKO<\/jats:sup>\n ) mice were generated via AAV9-cTnT-Cre delivery to\n Gabbr1<\/jats:italic>\n f\/f<\/jats:sup>\n mice. Cardiac sympathetic denervation was achieved by 6-hydroxydopamine (6-OHDA) treatment and sympathectomy. Mechanistic insights were obtained through Western blotting, immunofluorescence,\n in vivo<\/jats:italic>\n electrophysiology, and patch-clamp recordings.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n GLP-1RA increased the heart rate independent of the sympathetic input, suggesting a cardiac-autonomous mechanism. GABA\n B<\/jats:sub>\n R activation attenuated GLP-1RA-induced tachycardia, whereas Gabrb1 deficiency exacerbated it. GABA\n B<\/jats:sub>\n R agonism enhanced resistance to ventricular arrhythmias post-MI in a GLP-1RA-dependent manner. Patch-clamp analysis revealed that GABA\n B<\/jats:sub>\n R-induced repolarization can be suppressed by semaglutide in a dose-dependent manner, indicating the possible mechanism.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n GABA\n B<\/jats:sub>\n R activation counteracts GLP-1RA\u2019s chronotropic effects while synergistically enhancing anti-arrhythmic efficacy post-MI, highlighting a novel GABA\n B<\/jats:sub>\n R\/GLP-1R interaction in cardiac electrophysiology.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2025.1616181","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:24:57Z","timestamp":1761899097000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Agonizing GABABR suppresses GLP-1RA\u2019s chronotropic effect and reduces post-myocardial infarction arrhythmogenesis"],"prefix":"10.3389","volume":"16","author":[{"given":"Run","family":"Qi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhang","family":"Jingjing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gu","family":"Hongchang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chenyu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hu","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Juan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Yuqin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wu","family":"Xiaolin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/s41467-022-35716-1","article-title":"Revealing the tissue-level complexity of endogenous glucagon-like peptide-1 receptor expression and signaling","volume":"14","author":"Ast","year":"2023","journal-title":"Nat. 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