{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:40:03Z","timestamp":1784155203496,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,5,20]],"date-time":"2013-05-20T00:00:00Z","timestamp":1369008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["IZ73Z0_128016"],"award-info":[{"award-number":["IZ73Z0_128016"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030B_135693"],"award-info":[{"award-number":["310030B_135693"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Network for Translational Research in Atrial Fibrillation","award":["FP7"],"award-info":[{"award-number":["FP7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Na<jats:sub>v<\/jats:sub>1.5\u2010Arg689 in Arrhythmias<\/jats:title><jats:sec><jats:label\/><jats:p>Hundreds of genetic variants in <jats:italic>SCN5A<\/jats:italic>, the gene coding for the pore\u2010forming subunit of the cardiac sodium channel, Na<jats:sub>v<\/jats:sub>1.5, have been described in patients with cardiac channelopathies as well as in individuals from control cohorts. The aim of this study was to characterize the biophysical properties of 2 naturally occurring Na<jats:sub>v<\/jats:sub>1.5 variants, p.R689H and p.R689C, found in patients with cardiac arrhythmias and in control individuals. In addition, this study was motivated by the finding of the variant p.R689H in a family with sudden cardiac death (SCD) in children.<\/jats:p><jats:p>When expressed in HEK293 cells, most of the sodium current (I<jats:sub>Na<\/jats:sub>) biophysical properties of both variants were indistinguishable from the wild\u2010type (WT) channels. In both cases, however, an \u223c2\u2010fold increase of the tetrodotoxin\u2010sensitive late I<jats:sub>Na<\/jats:sub> was observed. Action potential simulations and reconstruction of pseudo\u2010ECGs demonstrated that such a subtle increase in the late I<jats:sub>Na<\/jats:sub> may prolong the QT interval in a nonlinear fashion. In conclusion, despite the fact that the causality link between p.R689H and the phenotype of the studied family cannot be demonstrated, this study supports the notion that subtle alterations of Na<jats:sub>v<\/jats:sub>1.5 variants may increase the risk for cardiac arrhythmias.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.12173","type":"journal-article","created":{"date-parts":[[2013,4,29]],"date-time":"2013-04-29T12:47:53Z","timestamp":1367239673000},"page":"1037-1046","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of 2 Genetic Variants of Na<sub>v<\/sub>1.5\u2010Arginine 689 Found in Patients with Cardiac Arrhythmias"],"prefix":"10.1111","volume":"24","author":[{"given":"VALENTIN","family":"SOTTAS","sequence":"first","affiliation":[{"name":"Department of Clinical Research University of Bern  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