{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:04:09Z","timestamp":1789470249737,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>\u03b2\u20103 adrenoceptor (AR) counteracts the \u03b2\u20101 and \u03b2\u20102 ARs and rescues the effects of excessive catecholamines. To test the hypothesis that a \u03b2\u20103 AR agonist (mirabegron) can reverse the effects of isoproterenol (ISO) on ventricular fibrillation (VF), we performed optical mapping studies in six male and six female Langendorff perfused rabbit hearts at baseline and after sequential administration of ISO (100\u00a0n<jats:sc>m<\/jats:sc>), mirabegron (1000\u00a0n<jats:sc>m<\/jats:sc>), apamin (100\u00a0n<jats:sc>m<\/jats:sc>) and washout (Study I). An additional six male and six female hearts were studied with mirabegron doses ranging between 250 and 1000\u00a0n<jats:sc>m<\/jats:sc> without ISO (Study II). Patch clamp studies in human embryonic kidney 293 cells were performed to determine the effect of mirabegron on the apamin\u2010sensitive small conductance Ca<jats:sup>2+<\/jats:sup> activated K<jats:sup>+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>KAS<\/jats:sub>). Study I show that ISO increased phase singularities per VF episode (PSs\/VF) in females and the dominant frequency (DF) in both sexes. Mirabegron significantly decreased PSs\/VF in both sexes and significantly decreased DF in females. Study II showed no significant difference in PSs\/VF between sexes at mirabegron concentrations of 250\u00a0n<jats:sc>m<\/jats:sc> and 500\u00a0n<jats:sc>m<\/jats:sc>. However, females showed significantly lower PSs\/VF than males at mirabegron concentrations of 750\u00a0n<jats:sc>m<\/jats:sc> and 1000\u00a0n<jats:sc>m<\/jats:sc>. There were no differences in the DF profiles of dose\u2013response between males and females. Mirabegron did not inhibit or activate <jats:italic>I<\/jats:italic><jats:sub>KAS<\/jats:sub> heterologously expressed in human embryonal kidney 293 cells. Reverse transcriptase\u2010quantitative PCR showed no differences in \u03b2\u20103 AR expression between sexes. We conclude that mirabegron is antiarrhythmic, and its antiarrhythmic properties are more commonly observed in females than males.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16594-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Sympathetic nerve activity activates \u03b2 adrenoceptors to induce cardiac arrhythmia. Among the \u03b2 adrenoceptors, \u03b2\u20103 counteracts the effects of \u03b2\u20101 and \u03b2\u20102.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Mirabegron is an US Food and Drug Administration (FDA)\u2010approved \u03b2\u20103 agonist that does not by itself block cardiac ionic currents or prolong the QT interval.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We showed that mirabegron significantly prevents wave breaks and reduces the dominant frequency of ventricular fibrillation. These effects are more prominent in female than in male rabbit ventricles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Because the FDA approves mirabegron for human use, its antiarrhythmic effects can be readily tested in humans.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp286901","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T04:59:27Z","timestamp":1742014767000},"page":"2533-2549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antiarrhythmic effects of mirabegron on ventricular fibrillation in Langendorff\u2010perfused rabbit ventricles"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7280-9226","authenticated-orcid":false,"given":"Xiao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiology Smidt Heart Institute, Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Ling","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Cardiology Smidt Heart Institute, Cedars\u2010Sinai Medical Center  Los Angeles CA USA"},{"name":"The Graduate Institute of Biomedical Optomechatronics Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7758-0355","authenticated-orcid":false,"given":"Liyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Smidt Heart Institute, Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Indiana University  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Smidt Heart Institute, Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2117-9463","authenticated-orcid":false,"given":"James E.","family":"Tisdale","sequence":"additional","affiliation":[{"name":"College of Pharmacy Purdue University  Indianapolis IN USA"},{"name":"Division of Clinical Pharmacology, Department of Medicine, School of Medicine Indiana University  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhui","family":"Chen","sequence":"additional","affiliation":[{"name":"the Krannert Cardiovascular Research Center and Division of Cardiology, Department of Medicine Indiana University  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua I.","family":"Goldhaber","sequence":"additional","affiliation":[{"name":"Department of Cardiology Smidt Heart Institute, Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rubart","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Indiana University  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4150-5836","authenticated-orcid":false,"given":"Peng\u2010Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Smidt Heart Institute, Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh2301.100801"},{"issue":"1","key":"e_1_2_5_3_1","first-page":"14","article-title":"Expression of G protein\u2010coupled receptors and related proteins in HEK293, AtT20, BV2, and N18 cell lines as revealed by microarray analysis","volume":"12","author":"Atwood B. 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