{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:54:31Z","timestamp":1790877271556,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["IFEQ21\/00012, PI23\/00182"],"award-info":[{"award-number":["IFEQ21\/00012, PI23\/00182"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aims to investigate whether the Fibroblast Growth Factor 23 (FGF23) modulates the electrical activity of sinoatrial (SAN) cells. The canonical function of FGF23 is to regulate body phosphorus and calcium homeostasis by activating the FGF1 receptors (FGFR1)\/\u03b1\u2010Klotho complex in the kidney and parathyroid glands. High levels of FGF23 can induce cardiac arrhythmias by affecting cardiomyocyte's function in an \u03b1\u2010Klotho independent manner. Although SAN cells are not traditionally considered targets of FGF23, the presence of \u03b1\u2010Klotho in pacemaker and not in ventricular cells has raised this possibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The effect of FGF23 was evaluated by patch\u2010clamp experiments on mouse SAN and on human\u2010induced pluripotent stem cells\u2010derived pacemaker\u2010like cardiomyocytes (hiPSC\u2010derived pCMs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our data reveal that mouse SAN cells express both membrane \u03b1\u2010Klotho and FGF23 receptors (FGFR) and that 48\u2009h tissue incubation with FGF23 (10\u2009ng\/mL) increases the spontaneous action potential (AP) frequency of these cells through an increase in the funny\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>f<\/jats:sub>\n                      current. Patch\u2010clamp experiments carried out using the pan\u2010FGFR inhibitor, PD173074, and SAN cells isolated from \u03b1\u2010Klotho hypomorphic mice suggested that FGF23 effects are mediated by the activation of the FGFR\u2010\u03b1\u2010Klotho complex. FGFRs expression data and FGF23\u2010induced electrical modification were further confirmed in hiPSC\u2010derived pCMs. Indeed, 48\u2009h incubation of these cells with FGF23 increases both the AP frequency, in a dose\u2010dependent manner, and the\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>f<\/jats:sub>\n                      current.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study represents the first evidence that FGF23 directly regulates the SAN electrical activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70293","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:37:57Z","timestamp":1788255477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Binding of Fibroblast Growth Factor 23 (\n                    <scp>FGF23<\/scp>\n                    ) to\n                    <scp>FGF<\/scp>\n                    Receptor\u2010\n                    <scp>\u03b1Klotho<\/scp>\n                    Complex Increases Sinoatrial Electrical Activity"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-253X","authenticated-orcid":false,"given":"Giorgia","family":"Bertoli","sequence":"first","affiliation":[{"name":"The Cell Physiology MiLab, Department of Biosciences Universit\u00e0 Degli Studi di Milano  Milan Italy"},{"name":"The Leon Charney Division of Cardiology New York University Grossmann School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-3301","authenticated-orcid":false,"given":"Patrizia","family":"Benzoni","sequence":"additional","affiliation":[{"name":"The Cell Physiology MiLab, Department of Biosciences 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