{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T23:07:25Z","timestamp":1782169645473,"version":"3.54.5"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T00:00:00Z","timestamp":1565222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/M014967\/1"],"award-info":[{"award-number":["MR\/M014967\/1"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1007260","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T13:29:13Z","timestamp":1565270953000},"page":"e1007260","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":46,"title":["Arrhythmia mechanisms and spontaneous calcium release: Bi-directional coupling between re-entrant and focal excitation"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2817-8508","authenticated-orcid":true,"given":"Michael A.","family":"Colman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,8,8]]},"reference":[{"issue":"35","key":"ref1","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1093\/eurheartj\/eht280","article-title":"Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060","volume":"34","author":"BP Krijthe","year":"2013","journal-title":"Eur Heart J"},{"key":"ref2","article-title":"The epidemiology of cardiovascular disease in the UK 2014","author":"P Bhatnagar","year":"2015","journal-title":"Heart"},{"key":"ref3","article-title":"Epidemiology and Management of Atrial Fibrillation and Stroke: Review of Data from Four European Countries","author":"AD Ceornodolea","year":"2017","journal-title":"Stroke Research and Treatment"},{"issue":"1","key":"ref4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev-physiol-021014-071622","article-title":"Mechanisms of Ventricular Arrhythmias: From Molecular Fluctuations to Electrical Turbulence","volume":"77","author":"Z Qu","year":"2015","journal-title":"Annu Rev Physiol"},{"issue":"6868","key":"ref5","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/415219a","article-title":"New ideas about atrial fibrillation 50 years on","volume":"415","author":"S Nattel","year":"2002","journal-title":"Nature"},{"issue":"4","key":"ref6","first-page":"528","article-title":"2012 HRS\/EHRA\/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design","volume":"14","author":"H Calkins","year":"2012","journal-title":"Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol"},{"issue":"2","key":"ref7","doi-asserted-by":"crossref","first-page":"e004549","DOI":"10.1161\/JAHA.112.004549","article-title":"Long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis","volume":"2","author":"AN Ganesan","year":"2013","journal-title":"J Am Heart Assoc"},{"key":"ref8","article-title":"Three-dimensional cardiac computational modelling: methods, features and applications","author":"A Lopez-Perez","year":"2015","journal-title":"Biomed Eng OnLine"},{"key":"ref9","article-title":"Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges","author":"M Vagos","year":"2018","journal-title":"Front Physiol"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pbiomolbio.2011.06.004","article-title":"Multi-scale modeling in biology: how to bridge the gaps between scales?","volume":"107","author":"Z Qu","year":"2011","journal-title":"Prog Biophys Mol Biol"},{"issue":"9","key":"ref11","first-page":"1561","article-title":"From the ryanodine receptor to cardiac arrhythmias","volume":"73","author":"DA Eisner","year":"2009","journal-title":"Circ J Off J Jpn Circ Soc"},{"issue":"15","key":"ref12","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/eurheartj\/ehs079","article-title":"The multidimensional role of calcium in atrial fibrillation pathophysiology: mechanistic insights and therapeutic opportunities","volume":"33","author":"S Nattel","year":"2012","journal-title":"Eur Heart J"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.yjmcc.2012.11.017","article-title":"Calcium flux balance in the heart","volume":"58","author":"D Eisner","year":"2013","journal-title":"J Mol Cell Cardiol"},{"issue":"2","key":"ref14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1161\/CIRCULATIONAHA.113.006641","article-title":"Cellular and molecular mechanisms of atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation","volume":"129","author":"N Voigt","year":"2014","journal-title":"Circulation"},{"issue":"12","key":"ref15","first-page":"1969","article-title":"Calcium Signaling and Cardiac Arrhythmias. Circ Res","volume":"120","author":"AP Landstrom","year":"2017","journal-title":"Calcium Signaling and Cardiac Arrhythmias. Circ Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev-physiol-021014-071622","article-title":"Mechanisms of ventricular arrhythmias: from molecular fluctuations to electrical turbulence","volume":"77","author":"Z Qu","year":"2015","journal-title":"Annu Rev Physiol"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/cvr\/cvr025","article-title":"The relationship between arrhythmogenesis and impaired contractility in heart failure: role of altered ryanodine receptor function","volume":"90","author":"AE Belevych","year":"2011","journal-title":"Cardiovasc Res"},{"issue":"5","key":"ref18","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.bpj.2010.06.042","article-title":"So little source, so much sink: requirements for afterdepolarizations to propagate in tissue","volume":"99","author":"Y Xie","year":"2010","journal-title":"Biophys J"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/cvr\/cvv149","article-title":"Stochastic spontaneous calcium release events trigger premature ventricular complexes by overcoming electrotonic load","volume":"107","author":"FO Campos","year":"2015","journal-title":"Cardiovasc Res"},{"issue":"9","key":"ref20","doi-asserted-by":"crossref","first-page":"093910","DOI":"10.1063\/1.4999612","article-title":"Stochastic spontaneous calcium release events and sodium channelopathies promote ventricular arrhythmias","volume":"27","author":"FO Campos","year":"2017","journal-title":"Chaos Woodbury N"},{"key":"ref21","first-page":"325","article-title":"From microscopic calcium sparks to the ECG: Model reduction approaches for multi-scale cardiac simulation","author":"MA Colman","year":"2015","journal-title":"In: 2015 Computing in Cardiology Conference (CinC)"},{"key":"ref22","article-title":"Trigger vs. Substrate: Multi-Dimensional Modulation of QT-Prolongation Associated Arrhythmic Dynamics by a hERG Channel Activator.","author":"MA Colman","year":"2017","journal-title":"Front Physiol"},{"issue":"11","key":"ref23","doi-asserted-by":"crossref","first-page":"e1005783","DOI":"10.1371\/journal.pcbi.1005783","article-title":"Estimating the probabilities of rare arrhythmic events in multiscale computational models of cardiac cells and tissue","volume":"13","author":"MA Walker","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"ref24","article-title":"Microscopic Isthmuses and Fibrosis Within the Border Zone of Infarcted Hearts Promote Calcium-Mediated Ectopy and Conduction Block","author":"FO Campos","year":"2018","journal-title":"Front Phys"},{"issue":"10","key":"ref25","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/j.hrthm.2015.06.019","article-title":"Delayed afterdepolarizations generate both triggers and a vulnerable substrate promoting reentry in cardiac tissue","volume":"12","author":"MB Liu","year":"2015","journal-title":"Heart Rhythm Off J Heart Rhythm Soc"},{"issue":"5","key":"ref26","doi-asserted-by":"crossref","first-page":"e1002061","DOI":"10.1371\/journal.pcbi.1002061","article-title":"Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation","volume":"7","author":"T O\u2019Hara","year":"2011","journal-title":"PLoS Comput Biol"},{"issue":"17","key":"ref27","doi-asserted-by":"crossref","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":"MA Colman","year":"2013","journal-title":"J Physiol"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"015105","DOI":"10.1063\/1.2404634","article-title":"Virtual cell and tissue dynamics of ectopic activation of the ventricles","volume":"17","author":"AP Benson","year":"2007","journal-title":"Chaos Interdiscip J Nonlinear Sci"},{"issue":"1\u20133","key":"ref29","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.pbiomolbio.2007.08.002","article-title":"The canine virtual ventricular wall: a platform for dissecting pharmacological effects on propagation and arrhythmogenesis","volume":"96","author":"AP Benson","year":"2008","journal-title":"Prog Biophys Mol Biol"},{"key":"ref30","first-page":"4324","article-title":"A framework for personalization of computational models of the human atria","volume":"2011","author":"O D\u00f6ssel","year":"2011","journal-title":"Conf Proc Annu Int Conf IEEE Eng Med Biol Soc IEEE Eng Med Biol Soc Annu Conf"},{"issue":"1","key":"ref31","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1109\/TMI.2012.2201948","article-title":"Personalization of atrial anatomy and electrophysiology as a basis for clinical modeling of radio-frequency ablation of atrial fibrillation","volume":"32","author":"MW Krueger","year":"2013","journal-title":"IEEE Trans Med Imaging"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"474","DOI":"10.3389\/fphys.2016.00474","article-title":"Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling","volume":"7","author":"R Morgan","year":"2016","journal-title":"Front Physiol"},{"issue":"8","key":"ref33","doi-asserted-by":"crossref","first-page":"e1005714","DOI":"10.1371\/journal.pcbi.1005714","article-title":"A computational model of spatio-temporal cardiac intracellular calcium handling with realistic structure and spatial flux distribution from sarcoplasmic reticulum and t-tubule reconstructions","volume":"13","author":"MA Colman","year":"2017","journal-title":"PLOS Comput Biol"},{"issue":"17","key":"ref34","doi-asserted-by":"crossref","first-page":"4289","DOI":"10.1113\/jphysiol.2012.235986","article-title":"Transient outward K+ current reduction prolongs action potentials and promotes afterdepolarisations: a dynamic-clamp study in human and rabbit cardiac atrial myocytes","volume":"590","author":"AJ Workman","year":"2012","journal-title":"J Physiol"},{"issue":"9","key":"ref35","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1161\/CIRCRESAHA.110.229294","article-title":"Variability in timing of spontaneous calcium release in the intact rat heart is determined by the time course of sarcoplasmic reticulum calcium load","volume":"107","author":"JA Wasserstrom","year":"2010","journal-title":"Circ Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.yjmcc.2017.12.003","article-title":"Transverse tubular network structures in the genesis of intracellular calcium alternans and triggered activity in cardiac cells","volume":"114","author":"Z Song","year":"2018","journal-title":"J Mol Cell Cardiol"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","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":"M Courtemanche","year":"1998","journal-title":"Am J Physiol-Heart Circ Physiol"},{"issue":"1","key":"ref38","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1161\/01.RES.0000252828.17939.00","article-title":"Increasing ryanodine receptor open probability alone does not produce arrhythmogenic calcium waves: threshold sarcoplasmic reticulum calcium content is required","volume":"100","author":"LA Venetucci","year":"2007","journal-title":"Circ Res"},{"issue":"1","key":"ref39","doi-asserted-by":"crossref","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":"VN Biktashev","year":"1998","journal-title":"Chaos Interdiscip J Nonlinear Sci"},{"issue":"6","key":"ref40","doi-asserted-by":"crossref","first-page":"e1005587","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":"MA Colman","year":"2017","journal-title":"PLOS Comput Biol"},{"key":"ref41","first-page":"221","article-title":"A new model of the human atrial myocyte with variable T-tubule organization for the study of atrial fibrillation","author":"MA Colman","year":"2016","journal-title":"In: 2016 Computing in Cardiology Conference (CinC)"},{"issue":"5","key":"ref42","doi-asserted-by":"crossref","first-page":"H1996","DOI":"10.1152\/ajpheart.00284.2011","article-title":"Transverse tubules are a common feature in large mammalian atrial myocytes including human","volume":"301","author":"MA Richards","year":"2011","journal-title":"Am J Physiol\u2014Heart Circ Physiol"},{"issue":"2","key":"ref43","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.hrthm.2016.09.022","article-title":"Regional Distribution of T-tubule Density in Left and Right Atria in Dogs","volume":"14","author":"R Arora","year":"2017","journal-title":"Heart Rhythm"},{"issue":"3","key":"ref44","doi-asserted-by":"crossref","first-page":"e17901","DOI":"10.1371\/journal.pone.0017901","article-title":"Changes in the organization of excitation-contraction coupling structures in failing human heart","volume":"6","author":"DJ Crossman","year":"2011","journal-title":"PloS One"},{"issue":"9","key":"ref45","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1002\/jcp.22559","article-title":"The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts","volume":"226","author":"OJ Kemi","year":"2011","journal-title":"J Cell Physiol"},{"issue":"2","key":"ref46","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/cvr\/cvt026","article-title":"Alterations in T-tubule and dyad structure in heart disease: challenges and opportunities for computational analyses","volume":"98","author":"E Pol\u00e1kov\u00e1","year":"2013","journal-title":"Cardiovasc Res"},{"issue":"1","key":"ref47","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1161\/01.RES.71.1.18","article-title":"Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy","volume":"71","author":"AM Brillantes","year":"1992","journal-title":"Circ Res"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1161\/01.RES.87.1.8","article-title":"Cardiac intracellular calcium release channels: role in heart failure","volume":"87","author":"AR Marks","year":"2000","journal-title":"Circ Res"},{"issue":"4","key":"ref49","doi-asserted-by":"crossref","first-page":"042719","DOI":"10.1103\/PhysRevE.91.042719","article-title":"Approximate analytical solutions for excitation and propagation in cardiac tissue","volume":"91","author":"D Greene","year":"2015","journal-title":"Phys Rev E"},{"issue":"9","key":"ref50","doi-asserted-by":"crossref","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":"E Grandi","year":"2011","journal-title":"Circ Res"},{"issue":"10","key":"ref51","doi-asserted-by":"crossref","first-page":"108101","DOI":"10.1103\/PhysRevLett.114.108101","article-title":"Calcium alternans is due to an order-disorder phase transition in cardiac cells","volume":"114","author":"E Alvarez-Lacalle","year":"2015","journal-title":"Phys Rev Lett"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T15:46:15Z","timestamp":1590075975000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007260"}},"subtitle":[],"editor":[{"given":"Patrick","family":"Boyle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,8,8]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1007260","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/434456","asserted-by":"object"},{"id-type":"doi","id":"10.1101\/434464","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,8]]}}}