{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:36:15Z","timestamp":1785864975769,"version":"3.56.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Life-threatening ventricular arrhythmias, typically arising from interfaces between fibrosis and surviving cardiomyocytes, are feared sequelae of structurally remodeled hearts under oxidative stress. Incomplete understanding of the proarrhythmic electrical remodeling by fibrosis limits the development of novel antiarrhythmic strategies. To define the mechanistic determinants of the proarrhythmia in electrical crosstalk between cardiomyocytes and noncardiomyocytes, we developed a novel <jats:italic>in vitro<\/jats:italic> model of interface between neonatal rat ventricular cardiomyocytes (NRVMs) and controls [NRVMs or connexin43 (Cx43)-deficient HeLa cells] vs. Cx43<jats:sup>+<\/jats:sup> noncardiomyocytes [aged rat ventricular myofibroblasts (ARVFs) or HeLaCx43 cells]. We performed high-speed voltage-sensitive optical imaging at baseline and following acute H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> exposure. In NRVM-NRVM and NRVM-HeLa controls, no arrhythmias occurred under either experimental condition. In the NRVM-ARVF and NRVM-HeLaCx43 groups, Cx43<jats:sup>+<\/jats:sup> noncardiomyocytes enabled passive decremental propagation of electrical impulses and impaired NRVM activation and repolarization, thereby slowing conduction and prolonging action potential duration. Following H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> exposure, arrhythmia triggers, automaticity, and non-reentrant and reentrant arrhythmias emerged. This study reveals that myofibroblasts (which generate cardiac fibrosis) and other noncardiomyocytes can induce not only structural remodeling but also electrical remodeling and that electrical remodeling by noncardiomyocytes can be particularly arrhythmogenic in the presence of an oxidative burst. Synergistic electrical remodeling between H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and noncardiomyocytes may account for the clinical arrhythmogenicity of myofibroblasts at fibrotic interfaces with cardiomyocytes in ischemic\/non-ischemic cardiomyopathies. Understanding the enhanced arrhythmogenicity of synergistic electrical remodeling by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and noncardiomyocytes may guide novel safe-by-design antiarrhythmic strategies for next-generation iatrogenic interfaces between surviving native cardiomyocytes and exogenous stem cells or engineered tissues in cardiac regenerative therapies.<\/jats:p>","DOI":"10.3389\/fphys.2020.622613","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T20:21:33Z","timestamp":1612297293000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Proarrhythmic Electrical Remodeling by Noncardiomyocytes at Interfaces With Cardiomyocytes Under Oxidative Stress"],"prefix":"10.3389","volume":"11","author":[{"given":"Yali","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankar","family":"Iyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Tavanaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole T.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao P.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.cardiores.2006.09.013","article-title":"Differential sensitivities of the NCX1.1 and NCX1.3 isoforms of the Na+-Ca2+ exchanger to alpha-linolenic acid","volume":"73","author":"Ander","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/s00249-008-0397-6","article-title":"Photogeneration of membrane potential hyperpolarization and depolarization in non-excitable cells","volume":"38","author":"Ando","year":"2009","journal-title":"Eur. Biophys. J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ccep.2010.10.012","article-title":"Overview of basic mechanisms of cardiac arrhythmia","volume":"3","author":"Antzelevitch","year":"2011","journal-title":"Card. Electrophysiol. Clin."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.yexcr.2008.12.021","article-title":"Cx43 contributes to TGF-beta signaling to regulate differentiation of cardiac fibroblasts into myofibroblasts","volume":"315","author":"Asazuma-Nakamura","year":"2009","journal-title":"Exp. Cell Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1074\/jbc.M111.316711","article-title":"Sulfiredoxin protein is critical for redox balance and survival of cells exposed to low steady-state levels of H2O2","volume":"287","author":"Baek","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"H2331","DOI":"10.1152\/ajpheart.00094.2012","article-title":"Enhanced sensitivity of aged fibrotic hearts to angiotensin II- and hypokalemia-induced early afterdepolarization-mediated ventricular arrhythmias","volume":"302","author":"Bapat","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1161\/CIRCRESAHA.118.310082","article-title":"Calcium signaling and reactive oxygen species in mitochondria","volume":"122","author":"Bertero","year":"","journal-title":"Circ. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41569-018-0044-6","article-title":"Metabolic remodelling in heart failure","volume":"15","author":"Bertero","year":"","journal-title":"Nat. Rev. Cardiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1161\/CIRCEP.110.958991","article-title":"Drug-induced torsade de pointes arrhythmias in the chronic AV block dog are perpetuated by focal activity","volume":"4","author":"Boulaksil","year":"2011","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.bbabio.2009.04.001","article-title":"The cardioprotective effects elicited by p66(Shc) ablation demonstrate the crucial role of mitochondrial ROS formation in ischemia\/reperfusion injury","volume":"1787","author":"Carpi","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"B11","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1093\/cvr\/cvu264","article-title":"Functional crosstalk between cardiac fibroblasts and adult cardiomyocytes by soluble mediators","volume":"105","author":"Cartledge","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1172\/JCI94996","article-title":"Physiological genomics identifies genetic modifiers of long QT syndrome type 2 severity","volume":"128","author":"Chai","year":"2018","journal-title":"J. Clin. Invest."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1093\/europace\/euq120","article-title":"Automaticity and conduction properties of bio-artificial pacemakers assessed in an in vitro monolayer model of neonatal rat ventricular myocytes","volume":"12","author":"Chan","year":"2010","journal-title":"Europace"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1159\/000486167","article-title":"Progressive Reduction in Myocyte Autophagy After Myocardial Infarction in Rabbits: Association with oxidative stress and left ventricular remodeling","volume":"44","author":"Chi","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/scrt308","article-title":"Human pluripotent stem cell-derived cardiomyocytes for heart regeneration, drug discovery and disease modeling: from the genetic, epigenetic, and tissue modeling perspectives","volume":"4","author":"Chow","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1161\/01.CIR.88.3.915","article-title":"Slow conduction in the infarcted human heart. 'Zigzag' course of activation","volume":"88","author":"De Bakker","year":"1993","journal-title":"Circulation"},{"key":"B17","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1161\/01.CIR.77.3.589","article-title":"Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation","volume":"77","author":"De Bakker","year":"1988","journal-title":"Circulation"},{"key":"B18","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1161\/01.RES.81.3.423","article-title":"Expression pattern of connexin gene products at the early developmental stages of the mouse cardiovascular system","volume":"81","author":"Delorme","year":"1997","journal-title":"Circ. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00232-007-9046-8","article-title":"Gap junction channels and cardiac impulse propagation","volume":"218","author":"Desplantez","year":"2007","journal-title":"J. Membr. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s00424-004-1250-0","article-title":"Cardiac connexins Cx43 and Cx45: formation of diverse gap junction channels with diverse electrical properties","volume":"448","author":"Desplantez","year":"2004","journal-title":"Pflugers Arch."},{"key":"B21","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cardiores.2005.05.020","article-title":"Partial cell fusion: a newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts","volume":"68","author":"Driesen","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1152\/physrev.00018.2001","article-title":"Free radicals in the physiological control of cell function","volume":"82","author":"Droge","year":"2002","journal-title":"Physiol. Rev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1083\/jcb.129.3.805","article-title":"Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells","volume":"129","author":"Elfgang","year":"1995","journal-title":"J. Cell Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1161\/01.RES.79.1.115","article-title":"Anisotropic activation spread in heart cell monolayers assessed by high-resolution optical mapping. Role of tissue discontinuities","volume":"79","author":"Fast","year":"1996","journal-title":"Circ. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1161\/01.RES.0000089258.40661.0C","article-title":"Coupling of cardiac electrical activity over extended distances by fibroblasts of cardiac origin","volume":"93","author":"Gaudesius","year":"2003","journal-title":"Circ. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.pharmthera.2017.10.001","article-title":"The immature electrophysiological phenotype of iPSC-CMs still hampers in vitro drug screening: special focus on I(K1)","volume":"183","author":"Goversen","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"H1269","DOI":"10.1152\/ajpheart.1988.255.6.H1269","article-title":"Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury","volume":"255","author":"Granger","year":"1988","journal-title":"Am. J. Physiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/cvr\/cvr189","article-title":"Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes","volume":"92","author":"He","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.stemcr.2018.01.012","article-title":"Low resting membrane potential and low inward rectifier potassium currents are not inherent features of hiPSC-derived cardiomyocytes","volume":"10","author":"Horv\u00e1th","year":"2018","journal-title":"Stem Cell Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1016\/j.bpj.2010.07.027","article-title":"Membrane potential depolarization as a triggering mechanism for Vpu-mediated HIV-1 release","volume":"99","author":"Hsu","year":"2010","journal-title":"Biophys. J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.yjmcc.2019.10.001","article-title":"Enhancement of human iPSC-derived cardiomyocyte maturation by chemical conditioning in a 3D environment","volume":"138","author":"Huang","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1161\/01.RES.88.5.529","article-title":"Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction","volume":"88","author":"Ide","year":"2001","journal-title":"Circ. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"H2040","DOI":"10.1152\/ajpheart.01298.2007","article-title":"Loading effect of fibroblast-myocyte coupling on resting potential, impulse propagation, and repolarization: insights from a microstructure model","volume":"294","author":"Jacquemet","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s00395-005-0529-4","article-title":"Electrical interaction of mechanosensitive fibroblasts and myocytes in the heart","volume":"100","author":"Kamkin","year":"2005","journal-title":"Basic Res. Cardiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"H1132","DOI":"10.1152\/ajpheart.01141.2002","article-title":"Cardiac myofibroblasts isolated from the site of myocardial infarction express endothelin de novo","volume":"285","author":"Katwa","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1006\/jmcc.1998.0673","article-title":"Electrophysiological properties of mechanosensitive atrial fibroblasts from chronic infarcted rat heart","volume":"30","author":"Kiseleva","year":"1998","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1046\/j.1540-8167.2002.00865.x","article-title":"Heterogeneous loss of connexin43 protein in nonischemic dilated cardiomyopathy with ventricular tachycardia","volume":"13","author":"Kitamura","year":"2002","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1161\/01.RES.83.8.795","article-title":"Slow conduction in cardiac tissue, II: effects of branching tissue geometry","volume":"83","author":"Kucera","year":"1998","journal-title":"Circ. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.4161\/cc.10.15.16870","article-title":"Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis: the seed and soil also needs \u201cfertilizer\u201d","volume":"10","author":"Lisanti","year":"2011","journal-title":"Cell Cycle"},{"key":"B40","doi-asserted-by":"publisher","first-page":"26744","DOI":"10.1038\/srep26744","article-title":"Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart","volume":"6","author":"Mahoney","year":"2016","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3094","DOI":"10.1093\/eurheartj\/ehx177","article-title":"Predictive value of telomere length on outcome following acute myocardial infarction: evidence for contrasting effects of vascular vs. blood oxidative stress","volume":"38","author":"Margaritis","year":"2017","journal-title":"Eur. Heart J."},{"key":"B42","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s11357-016-9933-y","article-title":"Mitochondria and oxidative stress in heart aging","volume":"38","author":"Mart\u00edn-Fern\u00e1ndez","year":"2016","journal-title":"Age"},{"key":"B43","doi-asserted-by":"publisher","first-page":"H443","DOI":"10.1152\/ajpheart.01218.2010","article-title":"Cell-to-cell coupling in engineered pairs of rat ventricular cardiomyocytes: relation between Cx43 immunofluorescence and intercellular electrical conductance","volume":"302","author":"McCain","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3791\/60909","article-title":"Isolation and characterization of adult cardiac fibroblasts and myofibroblasts","author":"Melzer","year":"2020","journal-title":"J. Vis. Exp"},{"key":"B45","first-page":"629","article-title":"Negative growth control of HeLa cells by connexin genes: connexin species specificity","volume":"55","author":"Mesnil","year":"1995","journal-title":"Cancer Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1161\/01.RES.0000214537.44195.a3","article-title":"Electrotonic modulation of cardiac impulse conduction by myofibroblasts","volume":"98","author":"Miragoli","year":"2006","journal-title":"Circ. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"8879","DOI":"10.1038\/s41598-019-45078-2","article-title":"Myofibroblast modulation of cardiac myocyte structure and function","volume":"9","author":"Nagaraju","year":"2019","journal-title":"Sci. Rep."},{"key":"B48","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.yjmcc.2013.10.018","article-title":"Cardiac fibrosis and arrhythmogenesis: the road to repair is paved with perils","volume":"70","author":"Nguyen","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1161\/CIRCEP.114.002451","article-title":"Repolarization reserve evolves dynamically during the cardiac action potential: effects of transient outward currents on early afterdepolarizations","volume":"8","author":"Nguyen","year":"2015","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1113\/JP271318","article-title":"Increased susceptibility of spontaneously hypertensive rats to ventricular tachyarrhythmias in early hypertension","volume":"594","author":"Nguyen","year":"2016","journal-title":"J. Physiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1093\/cvr\/cvr292","article-title":"Arrhythmogenic consequences of myofibroblast-myocyte coupling","volume":"93","author":"Nguyen","year":"2012","journal-title":"Cardiovasc Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.cmet.2015.07.008","article-title":"Reversal of mitochondrial transhydrogenase causes oxidative stress in heart failure","volume":"22","author":"Nickel","year":"2015","journal-title":"Cell Metab."},{"key":"B53","doi-asserted-by":"publisher","first-page":"14855","DOI":"10.1073\/pnas.0901923106","article-title":"Heterotypic gap junction channels as voltage-sensitive valves for intercellular signaling","volume":"106","author":"Palacios-Prado","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1111\/jce.13300","article-title":"Slow conduction through an arc of block: a basis for arrhythmia formation postmyocardial infarction","volume":"28","author":"Patterson","year":"2017","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"H390","DOI":"10.1152\/ajpheart.91531.2007","article-title":"Structural coupling of cardiomyocytes and noncardiomyocytes: quantitative comparisons using a novel micropatterned cell pair assay","volume":"295","author":"Pedrotty","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1093\/cvr\/cvp164","article-title":"Cardiac fibroblast paracrine factors alter impulse conduction and ion channel expression of neonatal rat cardiomyocytes","volume":"83","author":"Pedrotty","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1161\/CIRCULATIONAHA.115.016217","article-title":"Molecular basis of hypokalemia-induced ventricular fibrillation","volume":"132","author":"Pezhouman","year":"2015","journal-title":"Circulation"},{"key":"B58","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1093\/bjaceaccp\/mkm013","article-title":"Cardiac muscle physiology","volume":"7","author":"Pinnell","year":"2007","journal-title":"Continu. Educ. Anaesth. Crit. Care Pain"},{"key":"B59","doi-asserted-by":"publisher","first-page":"14852","DOI":"10.1073\/pnas.1611184114","article-title":"Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics","volume":"113","author":"Quinn","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B60","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1161\/CIRCRESAHA.117.312287","article-title":"Cardiac cell cycle activation as a strategy to improve iPSC-derived cardiomyocyte therapy","volume":"122","author":"Rhee","year":"2018","journal-title":"Circ. Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1126\/science.1130481","article-title":"Cell signaling. H2O2, a necessary evil for cell signaling","volume":"312","author":"Rhee","year":"2006","journal-title":"Science"},{"key":"B62","doi-asserted-by":"publisher","first-page":"3619","DOI":"10.1242\/jcs.200667","article-title":"Role of connexin 43 in different forms of intercellular communication - gap junctions, extracellular vesicles and tunnelling nanotubes","volume":"130","author":"Ribeiro-Rodrigues","year":"2017","journal-title":"J. Cell Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1093\/cvr\/cvx006","article-title":"Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes","volume":"113","author":"Rocchetti","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1093\/cvr\/cvx163","article-title":"Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart","volume":"114","author":"Rubart","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.reth.2019.06.004","article-title":"Cardiac regeneration with pluripotent stem cell-derived cardiomyocytes and direct cardiac reprogramming","volume":"11","author":"Sadahiro","year":"2019","journal-title":"Regen. Ther."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e004567","DOI":"10.1161\/CIRCEP.116.004567","article-title":"TGF-beta1 (Transforming Growth Factor-beta1) plays a pivotal role in cardiac myofibroblast arrhythmogenicity","volume":"10","author":"Salvarani","year":"2017","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1080\/15419060802014404","article-title":"Neonatal rat cardiomyocytes show characteristics of nonhomotypic gap junction channels","volume":"15","author":"Schulte","year":"2008","journal-title":"Cell Commun. Adhes."},{"key":"B68","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1161\/01.RES.62.4.811","article-title":"Influence of the passive anisotropic properties on directional differences in propagation following modification of the sodium conductance in human atrial muscle. A model of reentry based on anisotropic discontinuous propagation","volume":"62","author":"Spach","year":"1988","journal-title":"Circ. Res."},{"key":"B69","doi-asserted-by":"publisher","first-page":"4820","DOI":"10.1128\/IAI.64.11.4820-4825.1996","article-title":"Enteropathogenic Escherichia coli markedly decreases the resting membrane potential of Caco-2 and HeLa human epithelial cells","volume":"64","author":"Stein","year":"1996","journal-title":"Infect. Immun."},{"key":"B70","first-page":"101","article-title":"Immunochemical and electrophysiological characterization of murine connexin40 and\u221243 in mouse tissues and transfected human cells","volume":"64","author":"Traub","year":"1994","journal-title":"Eur. J. Cell Biol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.pbiomolbio.2007.03.014","article-title":"Influence of anisotropic conduction properties in the propagation of the cardiac action potential","volume":"94","author":"Valderr\u00e1bano","year":"2007","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1046\/j.1540-8167.2001.00662.x","article-title":"Pace mapping of postinfarction scar to detect ventricular tachycardia exit sites and zones of slow conduction","volume":"12","author":"Van Dessel","year":"2001","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1161\/CIRCRESAHA.110.227421","article-title":"Enhanced fibroblast-myocyte interactions in response to cardiac injury","volume":"107","author":"Vasquez","year":"2010","journal-title":"Circ. Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1007\/PL00000793","article-title":"Effects of myocardial ischemia and reperfusion on mitochondrial function and susceptibility to oxidative stress","volume":"58","author":"Venditti","year":"2001","journal-title":"Cell. Mol. Life Sci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1093\/oxfordjournals.eurheartj.a059928","article-title":"Myocardial changes in pressure overload-induced left ventricular hypertrophy. A study on tissue composition, polyploidization and multinucleation","volume":"12","author":"Vliegen","year":"1991","journal-title":"Eur. Heart J."},{"key":"B76","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1096\/fj.04-2882fje","article-title":"Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts","volume":"19","author":"Waghray","year":"2005","journal-title":"FASEB J."},{"key":"B77","doi-asserted-by":"publisher","first-page":"e1297","DOI":"10.1038\/cddis.2014.267","article-title":"Concentration-dependent wrestling between detrimental and protective effects of H2O2 during myocardial ischemia\/reperfusion","volume":"5","author":"Wang","year":"2014","journal-title":"Cell Death Dis."},{"key":"B78","doi-asserted-by":"publisher","first-page":"165","DOI":"10.3389\/fphys.2020.00165","article-title":"Combinatorial treatment of human cardiac engineered tissues with biomimetic cues induces functional maturation as revealed by optical mapping of action potentials and calcium transients","volume":"11","author":"Wong","year":"2020","journal-title":"Front. Physiol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1161\/CIRCRESAHA.108.183475","article-title":"Oxidative-stress-induced afterdepolarizations and calmodulin kinase II signaling","volume":"104","author":"Xie","year":"2009","journal-title":"Circ. Res."},{"key":"B80","doi-asserted-by":"publisher","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":"Xie","year":"2010","journal-title":"Biophys. J."},{"key":"B81","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1021\/mp800121f","article-title":"Endocytosis and membrane potential are required for HeLa cell uptake of R.I.-CKTat9, a retro-inverso Tat cell penetrating peptide","volume":"6","author":"Zhang","year":"2009","journal-title":"Mol. Pharm."},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa238.","article-title":"Adult zebrafish ventricular electrical gradients as tissue mechanisms of ECG patterns under baseline vs. oxidative stress","author":"Zhao","year":"2020","journal-title":"Cardiovasc. Res"},{"key":"B83","doi-asserted-by":"publisher","first-page":"3716","DOI":"10.1172\/JCI120849","article-title":"Mitochondrial dysfunction in pathophysiology of heart failure","volume":"128","author":"Zhou","year":"2018","journal-title":"J. Clin. Invest."},{"key":"B84","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"B85","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1089\/ten.tec.2017.0169","article-title":"Characterization and standardization of cultured cardiac fibroblasts for ex vivo models of heart fibrosis and heart ischemia","volume":"23","author":"Zhou","year":"2017","journal-title":"Tissue Eng. Part C Methods"},{"key":"B86","doi-asserted-by":"publisher","first-page":"4469","DOI":"10.1529\/biophysj.108.136473","article-title":"Electrotonic myofibroblast-to-myocyte coupling increases propensity to reentrant arrhythmias in two-dimensional cardiac monolayers","volume":"95","author":"Zlochiver","year":"2008","journal-title":"Biophys. J."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2020.622613\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T20:21:37Z","timestamp":1612297297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2020.622613\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":86,"alternative-id":["10.3389\/fphys.2020.622613"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2020.622613","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,2]]},"article-number":"622613"}}