{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:19:43Z","timestamp":1790320783151,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["EP\/J00958X\/1"],"award-info":[{"award-number":["EP\/J00958X\/1"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/J00958X\/1"],"award-info":[{"award-number":["EP\/J00958X\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"DOI":"10.3389\/fphys.2018.01402","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T04:26:11Z","timestamp":1538627171000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Human Atrial Arrhythmogenesis and Sinus Bradycardia in KCNQ1-Linked Short QT Syndrome: Insights From Computational Modelling"],"prefix":"10.3389","volume":"9","author":[{"given":"Dominic G.","family":"Whittaker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Colman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules C.","family":"Hancox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henggui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,10,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08367-2","article-title":"In silico investigation of a KCNQ1 mutation associated with short QT syndrome.","volume":"7","author":"Adeniran","year":"2017","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1161\/01.CIR.0000130409.72142.FE","article-title":"Mutation in the KCNQ1 gene leading to the short qt-interval syndrome.","volume":"109","author":"Bellocq","year":"2004","journal-title":"Circulation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1007\/978-3-540-72907-5-21","article-title":"\u201cEffects of geometry and architecture on re-entrant scroll wave dynamics in human virtual ventricular tissues,\u201d in","author":"Benson","year":"2007","journal-title":"Functional Imaging and Modeling of the Heart"},{"key":"B4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1063\/1.166307","article-title":"Reentrant waves and their elimination in a model of mammalian ventricular tissue.","volume":"8","author":"Biktashev","year":"1998","journal-title":"Chaos Interdiscip. J. Nonlinear Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1016\/j.jacc.2010.02.028","article-title":"In humans, chronic atrial fibrillation decreases the transient outward current and ultrarapid component of the delayed rectifier current differentially on each atria and increases the slow component of the delayed rectifier current in both.","volume":"55","author":"Caballero","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1161\/CIRCEP.113.000439","article-title":"Selective targeting of gain-of-function KCNQ1 mutations predisposing to atrial fibrillation.","volume":"6","author":"Campbell","year":"2013","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1126\/science.1077771","article-title":"KCNQ1 gain-of-function mutation in familial atrial fibrillation.","volume":"299","author":"Chen","year":"2003","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/jhg.2015.44","article-title":"Genetics of atrial fibrillation: from families to genomes.","volume":"61","author":"Christophersen","year":"2016","journal-title":"J. Hum. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4249","DOI":"10.1113\/jphysiol.2013.254987","article-title":"Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria.","volume":"591","author":"Colman","year":"2013","journal-title":"J. Physiol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005587.","article-title":"In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis.","volume":"13","author":"Colman","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"H301","DOI":"10.1152\/ajpheart.1998.275.1.H301","article-title":"Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model.","volume":"275","author":"Courtemanche","year":"1998","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/j.hrthm.2009.04.015","article-title":"Mutation in the S3 segment of KCNQ1 results in familial lone atrial fibrillation.","volume":"6","author":"Das","year":"2009","journal-title":"Heart Rhythm"},{"key":"B13","first-page":"123","article-title":"Action potential clamp and mefloquine sensitivity of recombinant \u201cI KS\u201d channels incorporating the V307L KCNQ1 mutation.","volume":"61","author":"El Harchi","year":"2010","journal-title":"J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2365","DOI":"10.1113\/JP273259","article-title":"Computational analysis of the human sinus node action potential: model development and effects of mutations.","volume":"595","author":"Fabbri","year":"2017","journal-title":"J. Physiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.jacc.2004.02.034","article-title":"Short QT syndrome: pharmacological treatment.","volume":"43","author":"Gaita","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.jacc.2011.03.038","article-title":"Long-term follow-up of patients with short qt syndrome.","volume":"58","author":"Giustetto","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1093\/cvr\/cvs313","article-title":"Chronic atrial fibrillation up-regulates \u03b21-adrenoceptors affecting repolarizing currents and action potential duration.","volume":"97","author":"Gonz\u00e1lez de la Fuente","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1161\/CIRCRESAHA.111.253955","article-title":"Human atrial action potential and Ca2+ model: sinus rhythm and chronic atrial fibrillation.","volume":"109","author":"Grandi","year":"2011","journal-title":"Circ. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1080\/14728222.2018.1470621.","article-title":"Emerging therapeutic targets in the short QT syndrome.","volume":"22","author":"Hancox","year":"2018","journal-title":"Expert Opin. Ther. Targets."},{"key":"B20","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.ijcard.2015.04.090","article-title":"Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome.","volume":"190","author":"Harrell","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.joa.2015.11.007","article-title":"Atrial arrhythmias in inherited arrhythmogenic disorders.","volume":"32","author":"Hasdemir","year":"2016","journal-title":"J. Arrhythmia"},{"key":"B22","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.cardiores.2005.06.023","article-title":"De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero.","volume":"68","author":"Hong","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.jacep.2016.11.013","article-title":"The phenotypic spectrum of a mutation hotspot responsible for the short QT syndrome.","volume":"3","author":"Hu","year":"2017","journal-title":"JACC Clin. Electrophysiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4501","DOI":"10.1113\/jphysiol.2012.229146","article-title":"Pro-arrhythmogenic effects of the S140G KCNQ1 mutation in human atrial fibrillation \u2013 insights from modelling.","volume":"590","author":"Kharche","year":"2012","journal-title":"J. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/978-3-642-21028-0-28","article-title":"\u201cModeling atrial fiber orientation in patient-specific geometries: a semi-automatic rule-based approach,\u201d in","author":"Krueger","year":"2011","journal-title":"Functional Imaging and Modeling of the Heart Lecture Notes in Computer Science"},{"key":"B26","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1007\/s40846-017-0257-x","article-title":"Pro-arrhythmogenic effects of the V141M KCNQ1 mutation in short QT syndrome and its potential therapeutic targets: insights from modeling.","volume":"37","author":"Lee","year":"2017","journal-title":"J. Med. Biol. Eng."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1124\/mol.106.031682","article-title":"Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter.","volume":"71","author":"Lerche","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1016\/j.hrthm.2007.07.022","article-title":"KCNQ1 mutation Q147R is associated with atrial fibrillation and prolonged QT interval.","volume":"4","author":"Lundby","year":"2007","journal-title":"Heart Rhythm"},{"key":"B29","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1093\/cvr\/cvv196","article-title":"A new KCNQ1 mutation at the S5 segment that impairs its association with KCNE1 is responsible for short QT syndrome.","volume":"107","author":"Moreno","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150761","article-title":"Parameterization for in-silico modeling of ion channel interactions with drugs.","volume":"11","author":"Moreno","year":"2016","journal-title":"PLoS One"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1161\/01.RES.83.12.1224","article-title":"Quinidine interactions with human atrial potassium channels.","volume":"83","author":"Nenov","year":"1998","journal-title":"Circ. Res."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00946","article-title":"Synergistic anti-arrhythmic effects in human atria with combined use of sodium blockers and acacetin.","volume":"8","author":"Ni","year":"2017","journal-title":"Front. Physiol."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131432","article-title":"Late sodium current in human atrial cardiomyocytes from patients in sinus rhythm and atrial fibrillation.","volume":"10","author":"Poulet","year":"2015","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4179","DOI":"10.1113\/jphysiol.2008.157511","article-title":"Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels.","volume":"586","author":"Restier","year":"2008","journal-title":"J. Physiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1017\/S1047951115001432","article-title":"Sinus bradycardia, junctional rhythm, and low-rate atrial fibrillation in short QT syndrome during 20 years of follow-up: three faces of the same genetic problem.","volume":"26","author":"Righi","year":"2016","journal-title":"Cardiol. Young"},{"key":"B36","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.cardiores.2005.03.026","article-title":"Short QT syndrome.","volume":"67","author":"Schimpf","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1007\/s004240100608","article-title":"Dependence of IKs biophysical properties on the expression system.","volume":"442","author":"Seebohm","year":"2001","journal-title":"Pfl\u00fcg. Arch."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1098\/rsta.2006.1781","article-title":"Heterogeneous three-dimensional anatomical and electrophysiological model of human atria.","volume":"364","author":"Seemann","year":"2006","journal-title":"Philos. Trans. R. Soc. Lond. Math. Phys. Eng. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1161\/CIRCULATIONAHA.105.543306","article-title":"Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve.","volume":"112","author":"Silva","year":"2005","journal-title":"Circulation"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2472","DOI":"10.1093\/eurheartj\/ehm339","article-title":"Pacemaker current (If) in the human sinoatrial node.","volume":"28","author":"Verkerk","year":"2007","journal-title":"Eur. Heart J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1159\/000360758","article-title":"Short QT syndrome manifesting with neonatal atrial fibrillation and bradycardia.","volume":"128","author":"Villafa\u00f1e","year":"2014","journal-title":"Cardiology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1109\/CIC.2015.7411045","article-title":"\u201cIn silico investigation of short QT syndrome-linked potassium channel mutations on electro-mechanical function of human atrial cells,\u201d in","author":"Whittaker","year":"2015","journal-title":"Proceedings of the 2015 Computing in Cardiology Conference (CinC)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00759","article-title":"Computational analysis of the mode of action of disopyramide and quinidine on hERG-linked short QT syndrome in human ventricles.","volume":"8","author":"Whittaker","year":"","journal-title":"Front. Physiol."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005593","article-title":"Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: insights from virtual human atria.","volume":"13","author":"Whittaker","year":"","journal-title":"PLoS Comput. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"394","DOI":"10.11909\/j.issn.1671-5411.2015.04.002","article-title":"Characterization of a Chinese KCNQ1 mutation (R259H) that shortens repolarization and causes short QT syndrome 2.","volume":"12","author":"Wu","year":"2015","journal-title":"J. Geriatr. Cardiol. JGC"},{"key":"B46","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.pbiomolbio.2007.07.020","article-title":"Repolarisation and vulnerability to re-entry in the human heart with short QT syndrome arising from KCNQ1 mutation\u2014a simulation study.","volume":"96","author":"Zhang","year":"2008","journal-title":"Prog. Biophys. Mol. Biol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphys.2018.01402\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T04:26:19Z","timestamp":1538627179000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphys.2018.01402\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,4]]},"references-count":46,"alternative-id":["10.3389\/fphys.2018.01402"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2018.01402","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,4]]},"article-number":"1402"}}