{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:33:45Z","timestamp":1781735625232,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,7,19]],"date-time":"2013-07-19T00:00:00Z","timestamp":1374192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministero Istruzione Universit\u00e0 e Ricerca","award":["PRIN2008"],"award-info":[{"award-number":["PRIN2008"]}]},{"name":"Ente Cassa di Risparmio di Firenze and Istituto Nazionale Ricerche Cardiovascolari"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Human Chronic Atrial Fibrillation and I<jats:sub>f<\/jats:sub><\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Despite the evidence that the hyperpolarization\u2010activated current (I<jats:sub>f<\/jats:sub>) is highly modulated in human cardiomyopathies, no definite data exist in chronic atrial fibrillation (cAF). We investigated the expression, function, and modulation of I<jats:sub>f<\/jats:sub> in human cAF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Right atrial samples were obtained from sinus rhythm (SR, n = 49) or cAF (duration &gt;1 year, n = 31) patients undergoing corrective cardiac surgery. Among f\u2010channel isoforms expressed in the human atrium (HCN1, 2 and 4), HCN4 mRNA levels measured by RT\u2010PCR were significantly reduced. However, protein expression was preserved in cAF compared to SR (+85% for HCN4); concurrently, miR\u20101 expression was significantly reduced. In patch\u2010clamped atrial myocytes, current\u2010specific conductance (g<jats:sub>f<\/jats:sub>) was significantly increased in cAF at voltages around the threshold for I<jats:sub>f<\/jats:sub> activation (\u221260 to \u221280 mV); accordingly, a 10\u2010mV rightward shift of the activation curve occurred (P\u2009&lt;\u20090.01). \u03b2\u2010Adrenergic and 5\u2010HT<jats:sub>4<\/jats:sub> receptor stimulation exerted similar effects on I<jats:sub>f<\/jats:sub> in cAF and SR cells, while the ANP\u2010mediated effect was significantly reduced (P\u2009&lt;\u20090.02), suggesting downregulation of natriuretic peptide signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In human cAF modifications in transcriptional and posttranscriptional mechanisms of HCN channels occur, associated with a slight yet significant gain\u2010of\u2010function of I<jats:sub>f<\/jats:sub>, which may contribute to enhanced atrial ectopy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.12212","type":"journal-article","created":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T06:54:55Z","timestamp":1371452095000},"page":"1391-1400","source":"Crossref","is-referenced-by-count":41,"title":["Chronic Atrial Fibrillation Alters the Functional Properties of I<sub>f<\/sub> in the Human Atrium"],"prefix":"10.1111","volume":"24","author":[{"given":"FRANCESCA","family":"STILLITANO","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine (C.I.M.M.B.A.) Department NEUROFARBA, University of Firenze  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GIUSEPPE","family":"LONARDO","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine (C.I.M.M.B.A.) Department NEUROFARBA, University of Firenze  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GABRIELE","family":"GIUNTI","sequence":"additional","affiliation":[{"name":"Department of 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