{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:57:10Z","timestamp":1785225430076,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL169610"],"award-info":[{"award-number":["R01HL169610"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n Ventricular arrhythmias are a major cause of sudden cardiac death and can occur when repolarization reserve is reduced by electrolyte imbalances and natural variation in ion\u2010channel expression. Long QT syndrome type 3 (LQT3), caused by a gain\u2010of\u2010function mutation in the voltage\u2010gated sodium channel, is an established exemplar; however clinical presentation of disease\u2010associated symptoms can vary substantially. Here we examined how electrolyte state and intrinsic variability in ionic current conductances collectively influence arrhythmia risk. We simulated a population of human ventricular myocytes, with the expression of the LQT3\u2010associated \u0394KPQ mutant. Each cell was paced under nine extracellular Na\n +<\/jats:sup>\n \/K\n +<\/jats:sup>\n combinations (hypo\/normal\/hyper) in presence of the \u0394KPQ mutant channel. Action potential duration (APD)\u00a0>\u00a0500\u00a0ms or the presence of an early afterdepolarization (EAD) defined \u2018susceptible\u2019 myocytes. In general cells with longer APD at baseline electrolyte conditions were more likely to be susceptible following altered extracellular Na\n +<\/jats:sup>\n or K\n +<\/jats:sup>\n concentrations. Susceptibility increased for reduced [K+]\n o<\/jats:sub>\n and elevated [Na+]\n o<\/jats:sub>\n . Interestingly across all nine conditions 50% of cells were never susceptible, 30% were susceptible in every condition, whereas 20% showed selective susceptibility (i.e. only susceptible to specific extracellular ionic conditions). Ionic current conductance profiles separated cells by susceptibility: non\u2010susceptible cells exhibited higher\n I<\/jats:italic>\n to<\/jats:sub>\n ,\n I<\/jats:italic>\n CaL<\/jats:sub>\n ,\n I<\/jats:italic>\n Kr<\/jats:sub>\n and\n I<\/jats:italic>\n Kb<\/jats:sub>\n , whereas susceptible cells had higher I\n K1<\/jats:sub>\n . Collectively these results connect common electrolyte disturbances and a critical set of ionic currents to condition\u2010dependent EADs and severe APD prolongation, and provide plausible mechanistic insight into the variable expression and incomplete penetrance of \u0394KPQ\u2010mediated LQT3.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Ventricular arrhythmias can arise in the setting of long QT syndrome type 3 (LQT3)\u2010associated mutations and are altered by electrolyte imbalance and natural ion\u2010channel variability.<\/jats:p>\n <\/jats:list-item>\n \n A population of human ventricular myocytes with LQT3 was simulated under nine conditions with altered extracellular sodium and potassium concentrations.<\/jats:p>\n <\/jats:list-item>\n \n Cells with longer baseline action potential duration (APD) were susceptible to early afterdepolarizations (EADs) and severe APD prolongation under hypokalaemia or hypernatraemia.<\/jats:p>\n <\/jats:list-item>\n \n Approximately 50% of cells were never susceptible, 30% were always susceptible and 20% were conditionally susceptible across the tested extracellular ionic conditions.<\/jats:p>\n <\/jats:list-item>\n \n Ionic current conductance profiles were associated with enhanced arrhythmia susceptibility.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290497","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:13:16Z","timestamp":1780474396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Extracellular ionic concentration modulates arrhythmias in a simulated population of human ventricular myocytes with long QT syndrome type 3"],"prefix":"10.1113","author":[{"given":"Katherine","family":"Flannery","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The Ohio State University Columbus Ohio USA"},{"name":"Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Ohio State University Columbus Ohio USA"},{"name":"Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6979-1264","authenticated-orcid":false,"given":"Steven","family":"Poelzing","sequence":"additional","affiliation":[{"name":"Translational Biology, Medicine, and Health Graduate Program Virginia Polytechnic Institute and State University Roanoke Virginia USA"},{"name":"Department of Biomedical Engineering and Mechanics Virginia Polytechnic Institute and State University Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1170-0419","authenticated-orcid":false,"given":"Seth H.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Ohio State University Columbus Ohio USA"},{"name":"Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"issue":"3","key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1001\/jama.2022.11176","article-title":"Diagnosis and management of hyponatremia: A review","volume":"328","author":"Adrogu\u00e9 H. J.","year":"2022","journal-title":"Journal of the American Medical Association"},{"issue":"3","key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1093\/cvr\/cvp083","article-title":"Re\u2010evaluating the efficacy of beta\u2010adrenergic agonists and antagonists in long QT\u20103 syndrome through computational modelling","volume":"82","author":"Ahrens\u2010Nicklas R. C.","year":"2009","journal-title":"Cardiovascular Research"},{"issue":"1","key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s13256-016-1062-9","article-title":"Extreme hypernatremia as a probable cause of fatal arrhythmia: A case report","volume":"10","author":"Arambewela M. H.","year":"2016","journal-title":"Journal of Medical Case Reports"},{"issue":"6","key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1113\/jphysiol.2014.279893","article-title":"Hypokalaemia induces Ca2+ overload and Ca2+ waves in ventricular myocytes by reducing Na+, K+\u2010ATPase \u03b12 activity","volume":"593","author":"Aronsen J. M.","year":"2015","journal-title":"The Journal of Physiology"},{"issue":"2","key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0008-6363(98)00021-2","article-title":"Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes","volume":"38","author":"Bosch R.","year":"1998","journal-title":"Cardiovascular Research"},{"issue":"23","key":"e_1_2_6_7_1","first-page":"E2098","article-title":"Experimentally calibrated population of models predicts and explains intersubject variability in cardiac cellular electrophysiology","volume":"110","author":"Britton O. J.","year":"2013","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.580481","article-title":"Ranolazine as an alternative therapy to flecainide for SCN5A V411M Long QT syndrome type 3 patients","volume":"11","author":"Cano J.","year":"2020","journal-title":"Frontiers in Pharmacology"},{"issue":"2","key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jemermed.2012.11.109","article-title":"Survival of acute hypernatremia due to massive soy sauce ingestion","volume":"45","author":"Carlberg D. J.","year":"2013","journal-title":"The Journal of Emergency Medicine"},{"key":"e_1_2_6_10_1","volume-title":"Goldman's Cecil medicine","author":"Cecil R. L.","year":"2012"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","DOI":"10.2196\/51003","article-title":"Use of epic electronic health record system for health care research: Scoping review","volume":"25","author":"Chishtie J.","year":"2023","journal-title":"Journal of Medical Internet Research"},{"issue":"6744","key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/23034","article-title":"Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia","volume":"400","author":"Clancy C. E.","year":"1999","journal-title":"Nature"},{"issue":"9","key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1172\/JCI0215928","article-title":"Insights into the molecular mechanisms of bradycardia\u2010triggered arrhythmias in long QT\u20103 syndrome","volume":"110","author":"Clancy C. E.","year":"2002","journal-title":"Journal of Clinical Investigation"},{"issue":"1","key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s43856-025-01260-4","article-title":"The effect of clinically relevant changes in extracellular electrolyte concentrations on human atrial arrhythmias","volume":"6","author":"Corrado C.","year":"2025","journal-title":"Communications Medicine"},{"issue":"1","key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000528375","article-title":"The SCN5A gene is a predictor of phenotype severity in Brugada syndrome: A comprehensive literature review","volume":"32","author":"Deica A. V.","year":"2023","journal-title":"Medical Principles and Practice"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2023.1164028","article-title":"Sex differences in long QT syndrome","volume":"10","author":"D\u00edez\u2010Escut\u00e9 N.","year":"2023","journal-title":"Frontiers in Cardiovascular Medicine"},{"issue":"4","key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"H963","DOI":"10.1152\/ajpheart.00792.2024","article-title":"Exploring the mechanisms of sex\u2010specific proarrhythmia in long QT syndrome through computational modeling","volume":"328","author":"Doherty I.","year":"2025","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"1","key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12937-023-00888-z","article-title":"Potassium levels and the risk of all\u2010cause and cardiovascular mortality among patients with cardiovascular diseases: A meta\u2010analysis of cohort studies","volume":"23","author":"Fan Y.","year":"2024","journal-title":"Nutrition Journal"},{"issue":"5","key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1136\/heart.88.5.475","article-title":"Increasing plasma potassium with amiloride shortens the QT interval and reduces ventricular extrasystoles but does not change endothelial function or heart rate variability in chronic heart failure","volume":"88","author":"Farquharson C. A. J.","year":"2002","journal-title":"Heart"},{"issue":"10","key":"e_1_2_6_20_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2025.e43396","article-title":"Reconsidering CPR protocols: Exploring hypernatremia's role in ventricular tachycardia from a case report","volume":"11","author":"Gavotto A.","year":"2025","journal-title":"Heliyon"},{"issue":"20","key":"e_1_2_6_21_1","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.124.034690","article-title":"Defining cardiomyocyte repolarization response to pharmacotherapy in long\u2010QT syndrome type 3","volume":"13","author":"Ge N.","year":"2024","journal-title":"Journal of the American Heart Association"},{"issue":"8","key":"e_1_2_6_22_1","first-page":"1254","article-title":"QT prolongation predicts short\u2010term mortality independent of comorbidity","volume":"21","author":"Gibbs C.","year":"2019","journal-title":"Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology"},{"issue":"1","key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2012.08.005","article-title":"Determinants of incomplete penetrance and variable expressivity in heritable cardiac arrhythmia syndromes","volume":"161","author":"Giudicessi J. R.","year":"2013","journal-title":"Translational Research"},{"issue":"2","key":"e_1_2_6_24_1","article-title":"Revealing the concealed nature of long\u2010QT type 3 syndrome","volume":"10","author":"Greer\u2010Short A.","year":"2017","journal-title":"Circulation: Arrhythmia and Electrophysiology"},{"issue":"2","key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1254\/jjp.76.149","article-title":"Shortening of monophasic action potential duration during hyperkalemia and myocardial ischemia in anesthetized dogs","volume":"76","author":"Hamada K.","year":"1998","journal-title":"Japanese Journal of Pharmacology"},{"issue":"12","key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1161\/CIRCRESAHA.116.304521","article-title":"The spectrum of epidemiology underlying sudden cardiac death","volume":"116","author":"Hayashi M.","year":"2015","journal-title":"Circulation Research"},{"issue":"8","key":"e_1_2_6_27_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1139\/cjpp-2019-0056","article-title":"Altered K+ current profiles underlie cardiac action potential shortening in hyperkalemia and \u03b2\u2010adrenergic stimulation","volume":"97","author":"Hegyi B.","year":"2019","journal-title":"Canadian Journal of Physiology and Pharmacology"},{"issue":"6","key":"e_1_2_6_28_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1161\/01.RES.41.6.799","article-title":"Transient, \u201cparadoxical\u201d effects of increasing extracellular K+ concentration on transmembrane potential in canine cardiac purkinje fibers. Role of the na+ pump and k+ conductance","volume":"41","author":"Ito S.","year":"1977","journal-title":"Circulation Research"},{"issue":"6","key":"e_1_2_6_29_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0097720","article-title":"Modeling tissue\u2010 and mutation\u2010 specific electrophysiological effects in the long QT syndrome: Role of the Purkinje fiber","volume":"9","author":"Iyer V.","year":"2014","journal-title":"PLoS ONE"},{"issue":"5","key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s11255-015-0969-1","article-title":"Extreme hypernatremia (254 mmol\/L) and electrocardiogram findings","volume":"47","author":"Kazanji N.","year":"2015","journal-title":"International Urology and Nephrology"},{"issue":"4","key":"e_1_2_6_31_1","first-page":"e96","article-title":"Hypokalemia and sudden cardiac death","volume":"15","author":"Kjeldsen K.","year":"2010","journal-title":"Experimental and Clinical Cardiology"},{"issue":"5","key":"e_1_2_6_32_1","first-page":"687","article-title":"Congenital Long QT syndrome","volume":"8","author":"Krahn A. D.","year":"2022","journal-title":"Journal of the American College of Cardiology: Clinical Electrophysiology"},{"issue":"1160","key":"e_1_2_6_33_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1136\/postgradmedj-2020-139701","article-title":"Diuretic\u2010induced hypokalaemia: An updated review","volume":"98","author":"Lin Z.","year":"2022","journal-title":"Postgraduate Medical Journal"},{"issue":"2","key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.amjcard.2009.08.676","article-title":"Mutation\u2010specific risk in two genetic forms of type 3 long QT syndrome","volume":"105","author":"Liu J. F.","year":"2010","journal-title":"The American Journal of Cardiology"},{"issue":"2","key":"e_1_2_6_35_1","doi-asserted-by":"crossref","DOI":"10.1136\/openhrt-2021-001670","article-title":"Effect of moderate potassium\u2010elevating treatment in long QT syndrome: The TriQarr Potassium Study","volume":"8","author":"Marstrand P.","year":"2021","journal-title":"Open Heart"},{"issue":"2","key":"e_1_2_6_36_1","doi-asserted-by":"crossref","first-page":"H179","DOI":"10.1152\/ajpheart.00430.2022","article-title":"Modeling incomplete penetrance in long QT syndrome type 3 through ion channel heterogeneity: An in silico population study","volume":"324","author":"Miller J. A.","year":"2023","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"7","key":"e_1_2_6_37_1","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1161\/CIRCRESAHA.113.301971","article-title":"Ranolazine for congenital and acquired late INa\u2010linked arrhythmias: In silico pharmacological screening","volume":"113","author":"Moreno J. D.","year":"2013","journal-title":"Circulation Research"},{"issue":"6","key":"e_1_2_6_38_1","first-page":"736","article-title":"A molecularly detailed NaV1.5 model reveals a new class I antiarrhythmic target","volume":"4","author":"Moreno J. D.","year":"2019","journal-title":"Journal of the American College of Cardiology: Basic to Translational Science"},{"issue":"11","key":"e_1_2_6_39_1","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1016\/j.bpj.2020.04.014","article-title":"Intercellular sodium regulates repolarization in cardiac tissue with sodium channel gain of function","volume":"118","author":"Nowak M. B.","year":"2020","journal-title":"Biophysical Journal"},{"key":"e_1_2_6_40_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.yjmcc.2020.12.008","article-title":"Mechanisms underlying age\u2010associated manifestation of cardiac sodium channel gain\u2010of\u2010function","volume":"153","author":"Nowak M. B.","year":"2021","journal-title":"Journal of Molecular and Cellular Cardiology"},{"issue":"3","key":"e_1_2_6_41_1","doi-asserted-by":"crossref","first-page":"98a","DOI":"10.1016\/j.bpj.2018.11.567","article-title":"Age dependent regulation of cardiac sodium channel gain of function","volume":"116","author":"Nowak M. B.","year":"2019","journal-title":"Biophysical Journal"},{"issue":"5","key":"e_1_2_6_42_1","doi-asserted-by":"crossref","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":"O'Hara T.","year":"2011","journal-title":"PLoS Computational Biology"},{"issue":"11","key":"e_1_2_6_43_1","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1016\/j.hrthm.2017.07.026","article-title":"Phenotypic variability in LQT3 human induced pluripotent stem cell\u2010derived cardiomyocytes and their response to antiarrhythmic pharmacologic therapy: An in silico approach","volume":"14","author":"Paci M.","year":"2017","journal-title":"Heart Rhythm"},{"key":"e_1_2_6_44_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.3389\/fphys.2017.00668","article-title":"Human In Silico drug trials demonstrate higher accuracy than animal models in predicting clinical pro\u2010arrhythmic cardiotoxicity","volume":"8","author":"Passini E.","year":"2017","journal-title":"Frontiers in Physiology"},{"key":"e_1_2_6_45_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.yjmcc.2015.09.003","article-title":"Mechanisms of pro\u2010arrhythmic abnormalities in ventricular repolarisation and anti\u2010arrhythmic therapies in human hypertrophic cardiomyopathy","volume":"96","author":"Passini E.","year":"2016","journal-title":"Journal of Molecular and Cellular Cardiology"},{"issue":"19","key":"e_1_2_6_46_1","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.1111\/bph.14786","article-title":"Drug\u2010induced shortening of the electromechanical window is an effective biomarker for in silico prediction of clinical risk of arrhythmias","volume":"176","author":"Passini E.","year":"2019","journal-title":"British Journal of Pharmacology"},{"issue":"6","key":"e_1_2_6_47_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0217432","article-title":"Association of hypokalemia with an increased risk for medically treated arrhythmias","volume":"14","author":"Phillips C. T.","year":"2019","journal-title":"PLoS ONE"},{"key":"e_1_2_6_48_1","article-title":"Comparative transcriptomics analysis of histone deacetylases, transcription factors, and ion channel genes in human iPSC\u2010cardiomyocytes vs. the adult human heart","volume":"6","author":"Pozo M. R.","year":"2026","journal-title":"The Journal of Precision Medicine: Health and Disease"},{"key":"e_1_2_6_49_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2021.697693","article-title":"Sensitivity analysis of ion channel conductance on myocardial electromechanical delay: Computational study","volume":"12","author":"Qauli A. I.","year":"2021","journal-title":"Frontiers in Physiology"},{"issue":"1879","key":"e_1_2_6_50_1","doi-asserted-by":"crossref","DOI":"10.1098\/rstb.2022.0164","article-title":"SCN5A channelopathy: Arrhythmia, cardiomyopathy, epilepsy and beyond","volume":"378","author":"Remme C. A.","year":"2023","journal-title":"Philosophical Transactions of the Royal Society B: Biological Sciences"},{"issue":"6","key":"e_1_2_6_51_1","doi-asserted-by":"crossref","first-page":"H1413","DOI":"10.1152\/ajpheart.00474.2024","article-title":"Connecting transcriptomics with computational modeling to reveal developmental adaptations in pediatric human atrial tissue","volume":"327","author":"Salameh S.","year":"2024","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"2","key":"e_1_2_6_52_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0092-8674(95)90340-2","article-title":"A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel","volume":"81","author":"Sanguinetti M. C.","year":"1995","journal-title":"Cell"},{"key":"e_1_2_6_53_1","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.3389\/fphys.2018.01500","article-title":"Hypokalemia\u2010induced arrhythmias and heart failure: New insights and implications for therapy","volume":"9","author":"Skogestad J.","year":"2018","journal-title":"Frontiers in Physiology"},{"issue":"2","key":"e_1_2_6_54_1","article-title":"Population modeling approach for human cardiac arrhythmia risk prediction","volume":"19","author":"Song Z.","year":"2026","journal-title":"Circulation: Arrhythmia and Electrophysiology"},{"issue":"7","key":"e_1_2_6_55_1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1161\/CIRCRESAHA.119.315641","article-title":"Hypokalemia promotes arrhythmia by distinct mechanisms in atrial and ventricular myocytes","volume":"126","author":"Tazmini K.","year":"2020","journal-title":"Circulation Research"},{"key":"e_1_2_6_56_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.48890","article-title":"Development, calibration, and validation of a novel human ventricular myocyte model in health, disease, and drug block","volume":"8","author":"Tomek J.","year":"2019","journal-title":"eLife"},{"issue":"10","key":"e_1_2_6_57_1","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCRESAHA.125.328073","article-title":"T\u2010world virtual human cardiomyocyte. I. Development, validation, and cell arrhythmogenesis","volume":"138","author":"Tomek J.","year":"2026","journal-title":"Circulation Research"},{"key":"e_1_2_6_58_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3389\/fphys.2014.00435","article-title":"Exploring susceptibility to atrial and ventricular arrhythmias resulting from remodeling of the passive electrical properties in the heart: A simulation approach","volume":"5","author":"Trayanova N. A.","year":"2014","journal-title":"Frontiers in Physiology"},{"issue":"4","key":"e_1_2_6_59_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.tcm.2017.11.002","article-title":"Pro\u2010arrhythmic effects of low plasma [K+] in human ventricle: An illustrated review","volume":"28","author":"Trenor B.","year":"2018","journal-title":"Trends in Cardiovascular Medicine"},{"issue":"37","key":"e_1_2_6_60_1","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2104019118","article-title":"Prediction of arrhythmia susceptibility through mathematical modeling and machine learning","volume":"118","author":"Varshneya M.","year":"2021","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"6","key":"e_1_2_6_61_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.31083\/j.rcm2506194","article-title":"Effects of acute hypernatremia on the electrophysiology of single human ventricular cardiomyocytes: An In silico study","volume":"25","author":"Verkerk A. O.","year":"2024","journal-title":"Reviews in Cardiovascular Medicine"},{"issue":"7","key":"e_1_2_6_62_1","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1007\/s00246-019-02151-x","article-title":"Long QT syndrome: Genetics and future perspective","volume":"40","author":"Wallace E.","year":"2019","journal-title":"Pediatric Cardiology"},{"issue":"3","key":"e_1_2_6_63_1","article-title":"Electrophysiology of hypokalemia and hyperkalemia","volume":"10","author":"Weiss J. N.","year":"2017","journal-title":"Circulation: Arrhythmia and Electrophysiology"},{"issue":"3","key":"e_1_2_6_64_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1177\/107424849700200307","article-title":"Modulation of the electrophysiologic actions of E\u20104031 and dofetilide by hyperkalemia and acidosis in Rabbit ventricular myocytes","volume":"2","author":"West P. D.","year":"1997","journal-title":"Journal of Cardiovascular Pharmacology and Therapeutics"},{"issue":"5","key":"e_1_2_6_65_1","first-page":"919","article-title":"Age\u2010associated perinexal narrowing masks consequences of sodium channel gain of function in Guinea pig hearts","volume":"11","author":"Wu X.","year":"2025","journal-title":"Journal of the American College of Cardiology: Clinical Electrophysiology"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP290497","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP290497","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP290497","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:13:24Z","timestamp":1780474404000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP290497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":64,"alternative-id":["10.1113\/JP290497"],"URL":"https:\/\/doi.org\/10.1113\/jp290497","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"2025-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"JP290497"}}