{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:10:24Z","timestamp":1792725024139,"version":"4.5.0"},"reference-count":58,"publisher":"Canadian Science Publishing","issue":"10","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p> Background. Mutations in the SCN5A gene have been linked to Brugada syndrome (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and to pre- and neonatal ventricular arrhythmias. Objective. The objective of this study is to characterize a novel mutation in Na<jats:sub>v<\/jats:sub>1.5 found in a newborn with fetal chaotic atrial tachycardia, post-partum intraventricular conduction delay, and QT interval prolongation. Methods. Genomic DNA was isolated and all exons and intron borders of 15 ion-channel genes were sequenced, revealing a novel missense mutation (Q270K) in SCN5A. Na<jats:sub>v<\/jats:sub>1.5 wild type (WT) and Q270K were expressed in CHO-K1 with and without the Na<jats:sub>v<\/jats:sub>\u03b21 subunit. Results. Patch-clamp analysis showed \u223c40% reduction in peak sodium channel current (I<jats:sub>Na<\/jats:sub>) density for Q270K compared with WT. Fast and slow decay of I<jats:sub>Na<\/jats:sub> were significantly slower in Q270K. Steady-state activation and inactivation of Q270K channels were shifted to positive potentials, and window current was increased. The tetrodotoxin-sensitive late I<jats:sub>Na<\/jats:sub> was increased almost 3-fold compared with WT channels. Ranolazine reduced late I<jats:sub>Na<\/jats:sub> in WT and Q270K channels, while exerting minimal effects on peak I<jats:sub>Na<\/jats:sub>. Conclusion. The Q270K mutation in SCN5A reduces peak I<jats:sub>Na<\/jats:sub> while augmenting late I<jats:sub>Na<\/jats:sub>, and may thus underlie the development of atrial tachycardia, intraventricular conduction delay, and QT interval prolongation in an infant. <\/jats:p>","DOI":"10.1139\/y11-070","type":"journal-article","created":{"date-parts":[[2011,9,23]],"date-time":"2011-09-23T14:48:30Z","timestamp":1316789310000},"page":"723-736","source":"Crossref","is-referenced-by-count":11,"title":["Multiple arrhythmic syndromes in a newborn, owing to a novel mutation in <i>SCN5A<\/i>"],"prefix":"10.1139","volume":"89","author":[{"given":"Kirstine","family":"Calloe","sequence":"first","affiliation":[{"name":"Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soren","family":"Grubb","sequence":"additional","affiliation":[{"name":"Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Pfeiffer","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens-Peter","family":"David","sequence":"additional","affiliation":[{"name":"Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Kanter","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Antzelevitch","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.08.025"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.18.2264"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000152479.54298.51"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.658021"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1007\/BF00586939"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001258"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.03.066"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2008.07.013"},{"issue":"12","key":"refg9\/ref9","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1161\/01.RES.85.12.1206","volume":"85","author":"Bezzina C.","year":"1999","journal-title":"Circ. 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