{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:19:34Z","timestamp":1788297574297,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T00:00:00Z","timestamp":1684022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004923","name":"AFM-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","award":["20002"],"award-info":[{"award-number":["20002"]}],"id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p><jats:italic>Nfix<\/jats:italic> is a transcription factor belonging to the <jats:italic>Nuclear Factor I<\/jats:italic> (NFI) family comprising four members (<jats:italic>Nfia<\/jats:italic>, <jats:italic>b<\/jats:italic>, <jats:italic>c<\/jats:italic>, <jats:italic>x<\/jats:italic>). <jats:italic>Nfix<\/jats:italic> plays important roles in the development and function of several organs. In muscle development<jats:italic>, Nfix<\/jats:italic> controls the switch from embryonic to fetal myogenesis by promoting fast twitching fibres. In the adult muscle, following injury, lack of <jats:italic>Nfix<\/jats:italic> impairs regeneration, inducing higher content of slow\u2010twitching fibres. <jats:italic>Nfix<\/jats:italic> is expressed also in the heart, but its function has been never investigated before. We studied <jats:italic>Nfix<\/jats:italic> role in this organ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using <jats:italic>Nfix<\/jats:italic>\u2010null and wild type (WT) mice we analyzed: (1) the expression pattern of <jats:italic>Nfix<\/jats:italic> during development by qPCR and (2) the functional alterations caused by its absence, by in vivo telemetry and in vitro patch clamp analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Conclusions<\/jats:title><jats:p><jats:italic>Nfix<\/jats:italic> expression start in the heart from E12.5. Adult hearts of <jats:italic>Nfix<\/jats:italic>\u2010null mice show a hearts morphology and sarcomeric proteins expression similar to WT. However, <jats:italic>Nfix<\/jats:italic>\u2010null animals show tachycardia that derives form an intrinsic higher beating rate of the sinus node (SAN). Molecular and functional analysis revealed that sinoatrial cells of <jats:italic>Nfix<\/jats:italic>\u2010null mice express a significantly larger L\u2010type calcium current (<jats:italic>Cacna1d<\/jats:italic>\u2009+\u2009<jats:italic>Cacna1c<\/jats:italic>). Interestingly, downregulation of <jats:italic>Nfix<\/jats:italic> by sh\u2010RNA in primary cultures of neonatal rat ventricular cardiomyocytes induced a similar increase in their spontaneous beating rate and in <jats:italic>I<\/jats:italic><jats:sub>CaL<\/jats:sub> current. In conclusion, our data provide the first demonstration of a role of <jats:italic>Nfix<\/jats:italic> that, increasing the L\u2010type calcium current, modulates heart rate.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13981","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T04:48:29Z","timestamp":1682484509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Lack of the transcription factor <i>Nfix<\/i> causes tachycardia in mice sinus node and rats neonatal cardiomyocytes"],"prefix":"10.1111","volume":"239","author":[{"given":"Sara","family":"Landi","sequence":"first","affiliation":[{"name":"The Cell Physiology MiLab, Department of Biosciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Giannetti","sequence":"additional","affiliation":[{"name":"The Cell Physiology MiLab, Department of 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