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ETV1, a key transcription factor regulating atrial electrical conduction, might also be involved in FGF23\u2010mediated AF. In this study, FGF23 intervention models were established via tail vein injection in mice and direct administration in vitro. ETV1 knockdown and overexpression were achieved in vitro using lentiviral vectors, and ETV1 knockout mice were generated. Patch\u2010clamp electrophysiology, calcium imaging and western blotting were performed to assess electrophysiological properties and AF susceptibility. Functionally, FGF23 increased both peak and residual sodium current measured 3\u00a0ms after peak activation, while also enhancing L\u2010type calcium current, prolonging action potential duration and promoting early and delayed after\u2010depolarizations. Consistent with these electrophysiological changes, Nav1.5 and RyR2 expression levels were upregulated, accompanied by increased intracellular calcium transients, thereby leading to increased AF susceptibility. In mechanistic analyses, ETV1 knockdown attenuated FGF23\u2010induced increases in sodium current and action potential parameters but did not reduce AF susceptibility, whereas ETV1 knockout increased AF inducibility. These findings suggest that FGF23 promotes AF by inducing coordinated electrical and calcium handling abnormalities that facilitate triggered activity, while ETV1 contributes to FGF23\u2010induced sodium channel regulation.<\/jats:p>","DOI":"10.1113\/ep093891","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T21:01:20Z","timestamp":1787605280000},"page":"4435-4456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FGF23 promotes atrial fibrillation susceptibility through ETV1\u2010dependent sodium channel regulation and calcium handling abnormalities"],"prefix":"10.1113","volume":"111","author":[{"given":"Qiaoting","family":"Yu","sequence":"first","affiliation":[{"name":"Shengli Clinical Medical College Fujian Medical University Fuzhou Fujian PR China"},{"name":"Department of Cardiology Shengli Clinical Medicine College of Fujian Medical University Fuzhou University Affiliated 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