{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:37:47Z","timestamp":1775885867327,"version":"3.50.1"},"reference-count":34,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","heartrhythmjournal.com","clinicalkey.es","clinicalkey.fr","clinicalkey.com.au","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Heart Rhythm"],"published-print":{"date-parts":[[2019,7]]},"DOI":"10.1016\/j.hrthm.2019.01.018","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T18:50:29Z","timestamp":1548096629000},"page":"1091-1097","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"title":["Multiple mechanisms underlie increased cardiac late sodium current"],"prefix":"10.1016","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6215-0803","authenticated-orcid":false,"given":"Brett M.","family":"Kroncke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan M.","family":"Roden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.hrthm.2019.01.018_bib1","doi-asserted-by":"crossref","first-page":"e002095","DOI":"10.1161\/CIRCGEN.118.002095","article-title":"SCN5A (NaV1.5) variant functional perturbation and clinical presentation: variants of a certain significance","volume":"11","author":"Kroncke","year":"2018","journal-title":"Circ Genom Precis Med"},{"key":"10.1016\/j.hrthm.2019.01.018_bib2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/hmg\/11.3.337","article-title":"Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome","volume":"11","author":"Vatta","year":"2002","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.hrthm.2019.01.018_bib3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0828-282X(06)70915-1","article-title":"Nav1.5\/R1193Q polymorphism is associated with both long QT and Brugada syndromes","volume":"22","author":"Huang","year":"2006","journal-title":"Can J Cardiol"},{"key":"10.1016\/j.hrthm.2019.01.018_bib4","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1136\/jmg.2003.013300","article-title":"The common SCN5A mutation R1193Q causes LQTS-type electrophysiological alterations of the cardiac sodium channel","volume":"41","author":"Wang","year":"2004","journal-title":"J Med Genet"},{"key":"10.1016\/j.hrthm.2019.01.018_bib5","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.hrthm.2005.04.021","article-title":"Common human SCN5A polymorphisms have altered electrophysiology when expressed in Q1077 splice variants","volume":"2","author":"Tan","year":"2005","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hrthm.2019.01.018_bib6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.hrthm.2019.01.018_bib7","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1038\/gim.2017.26","article-title":"Using high-resolution variant frequencies to empower clinical genome interpretation","volume":"19","author":"Whiffin","year":"2017","journal-title":"Genet Med"},{"key":"10.1016\/j.hrthm.2019.01.018_bib8","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.hrthm.2005.01.020","article-title":"Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing","volume":"2","author":"Tester","year":"2005","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hrthm.2019.01.018_bib9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"10.1016\/j.hrthm.2019.01.018_bib10","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/376683a0","article-title":"Molecular mechanism for an inherited cardiac arrhythmia","volume":"376","author":"Bennett","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.hrthm.2019.01.018_bib11","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1093\/hmg\/4.9.1603","article-title":"Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia","volume":"4","author":"Wang","year":"1995","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.hrthm.2019.01.018_bib12","doi-asserted-by":"crossref","first-page":"13200","DOI":"10.1073\/pnas.93.23.13200","article-title":"Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome","volume":"93","author":"Wang","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.hrthm.2019.01.018_bib13","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1124\/jpet.117.246157","article-title":"Inhibition of the \u03b1-subunit of phosphoinositide 3-kinase in heart increases late sodium current and is arrhythmogenic","volume":"365","author":"Yang","year":"2018","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.hrthm.2019.01.018_bib14","doi-asserted-by":"crossref","first-page":"131ra150","DOI":"10.1126\/scitranslmed.3003623","article-title":"Suppression of phosphoinositide 3-kinase signaling and alteration of multiple ion currents in drug-induced long QT syndrome","volume":"4","author":"Lu","year":"2012","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.hrthm.2019.01.018_bib15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.tcm.2015.05.006","article-title":"Late sodium current: a mechanism for angina, heart failure, and arrhythmia","volume":"26","author":"Makielski","year":"2016","journal-title":"Trends Cardiovasc Med"},{"key":"10.1016\/j.hrthm.2019.01.018_bib16","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1161\/01.CIR.0000014448.19052.4C","article-title":"Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes","volume":"105","author":"Yang","year":"2002","journal-title":"Circulation"},{"key":"10.1016\/j.hrthm.2019.01.018_bib17","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1113\/jphysiol.1984.sp015493","article-title":"The effects of the Anemonia sulcata toxin (ATX II) on membrane currents of isolated mammalian myocytes","volume":"357","author":"Isenberg","year":"1984","journal-title":"J Physiol"},{"key":"10.1016\/j.hrthm.2019.01.018_bib18","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1097\/00005344-200408000-00008","article-title":"Antagonism by ranolazine of the pro-arrhythmic effects of increasing late INa in guinea pig ventricular myocytes","volume":"44","author":"Song","year":"2004","journal-title":"J Cardiovasc Pharmacol"},{"key":"10.1016\/j.hrthm.2019.01.018_bib19","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/nmeth.2999","article-title":"Chemically defined generation of human cardiomyocytes","volume":"11","author":"Burridge","year":"2014","journal-title":"Nat Methods"},{"key":"10.1016\/j.hrthm.2019.01.018_bib20","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1161\/CIRCRESAHA.112.265173","article-title":"Blocking Scn10a channels in heart reduces late sodium current and is antiarrhythmic","volume":"111","author":"Yang","year":"2012","journal-title":"Circ Res"},{"key":"10.1016\/j.hrthm.2019.01.018_bib21","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1161\/CIRCULATIONAHA.113.007765","article-title":"Screening for acute IKr block is insufficient to detect torsades de pointes liability: role of late sodium current","volume":"130","author":"Yang","year":"2014","journal-title":"Circulation"},{"key":"10.1016\/j.hrthm.2019.01.018_bib22","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.cell.2017.06.039","article-title":"Structure of the Nav1.4-\u03b21 complex from electric eel","volume":"170","author":"Yan","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.hrthm.2019.01.018_bib23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0005-2736(87)90124-6","article-title":"A mechanistic interpretation of the action of toxin II from Anemonia sulcata on the cardiac sodium channel","volume":"901","author":"Schreibmayer","year":"1987","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.hrthm.2019.01.018_bib24","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1113\/jphysiol.1992.sp019225","article-title":"A persistent sodium current in rat ventricular myocytes","volume":"453","author":"Saint","year":"1992","journal-title":"J Physiol"},{"key":"10.1016\/j.hrthm.2019.01.018_bib25","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1098\/rspb.1994.0065","article-title":"Inactivation-resistant channels underlying the persistent sodium current in rat ventricular myocytes","volume":"256","author":"Ju","year":"1994","journal-title":"Proc Biol Sci"},{"key":"10.1016\/j.hrthm.2019.01.018_bib26","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3389\/fphar.2013.00126","article-title":"Sodium overload due to a persistent current that attenuates the arrhythmogenic potential of a novel LQT3 mutation","volume":"4","author":"Moreau","year":"2013","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.hrthm.2019.01.018_bib27","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1161\/01.RES.78.5.916","article-title":"Multiple mechanisms of Na+ channel\u2013linked long-QT syndrome","volume":"78","author":"Dumaine","year":"1996","journal-title":"Circ Res"},{"key":"10.1016\/j.hrthm.2019.01.018_bib28","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.febslet.2009.02.007","article-title":"Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS infant linked to long QT syndrome","volume":"583","author":"Huang","year":"2009","journal-title":"FEBS Lett"},{"key":"10.1016\/j.hrthm.2019.01.018_bib29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/jce.12270","article-title":"Cardiac channelopathies associated with infantile fatal ventricular arrhythmias: from the cradle to the bench","volume":"25","author":"Kato","year":"2014","journal-title":"J Cardiovasc Electrophysiol"},{"key":"10.1016\/j.hrthm.2019.01.018_bib30","doi-asserted-by":"crossref","first-page":"e1258","DOI":"10.1371\/journal.pone.0001258","article-title":"A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic response","volume":"2","author":"Bankston","year":"2007","journal-title":"PLoS One"},{"key":"10.1016\/j.hrthm.2019.01.018_bib31","doi-asserted-by":"crossref","first-page":"10910","DOI":"10.1073\/pnas.89.22.10910","article-title":"A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation","volume":"89","author":"West","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.hrthm.2019.01.018_bib32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1085\/jgp.201310998","article-title":"Domain IV voltage-sensor movement is both sufficient and rate limiting for fast inactivation in sodium channels","volume":"142","author":"Capes","year":"2013","journal-title":"J Gen Physiol"},{"key":"10.1016\/j.hrthm.2019.01.018_bib33","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1021\/bi9823380","article-title":"Solution structure of the sodium channel inactivation gate","volume":"38","author":"Rohl","year":"1999","journal-title":"Biochemistry"},{"key":"10.1016\/j.hrthm.2019.01.018_bib34","doi-asserted-by":"crossref","DOI":"10.1126\/science.aal4326","article-title":"Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution","volume":"355","author":"Shen","year":"2017","journal-title":"Science"}],"container-title":["Heart Rhythm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1547527119300311?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1547527119300311?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T04:21:37Z","timestamp":1561695697000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1547527119300311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["S1547527119300311"],"URL":"https:\/\/doi.org\/10.1016\/j.hrthm.2019.01.018","relation":{},"ISSN":["1547-5271"],"issn-type":[{"value":"1547-5271","type":"print"}],"subject":[],"published":{"date-parts":[[2019,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Multiple mechanisms underlie increased cardiac late sodium current","name":"articletitle","label":"Article Title"},{"value":"Heart Rhythm","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.hrthm.2019.01.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Heart Rhythm Society. All rights reserved.","name":"copyright","label":"Copyright"}]}}