{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:48:41Z","timestamp":1790189321995,"version":"4.1.0"},"reference-count":49,"publisher":"Rockefeller University Press","issue":"7","license":[{"start":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T00:00:00Z","timestamp":1527033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2018,12,30]],"date-time":"2018-12-30T00:00:00Z","timestamp":1546128000000},"content-version":"vor","delay-in-days":221,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of H","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ealth","award":["R01-HL074045"],"award-info":[{"award-number":["R01-HL074045"]}]},{"name":"ealth","award":["R01-HL063043"],"award-info":[{"award-number":["R01-HL063043"]}]},{"name":"ealth","award":["R01-HL138579"],"award-info":[{"award-number":["R01-HL138579"]}]},{"name":"ealth","award":["R00-HL127299"],"award-info":[{"award-number":["R00-HL127299"]}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,7,2]]},"abstract":"<jats:p>Recent evidence suggests that neuronal Na+ channels (nNavs) contribute to catecholamine-promoted delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardia (CPVT). The newly identified overlap between CPVT and long QT (LQT) phenotypes has stoked interest in the cross-talk between aberrant Na+ and Ca2+ handling and its contribution to early afterdepolarizations (EADs) and DADs. Here, we used Ca2+ imaging and electrophysiology to investigate the role of Na+ and Ca2+ handling in DADs and EADs in wild-type and cardiac calsequestrin (CASQ2)-null mice. In experiments, repolarization was impaired using 4-aminopyridine (4AP), whereas the L-type Ca2+ and late Na+ currents were augmented using Bay K 8644 (BayK) and anemone toxin II (ATX-II), respectively. The combination of 4AP and isoproterenol prolonged action potential duration (APD) and promoted aberrant Ca2+ release, EADs, and DADs in wild-type cardiomyocytes. Similarly, BayK in the absence of isoproterenol induced the same effects in CASQ2-null cardiomyocytes. In vivo, it prolonged the QT interval and, upon catecholamine challenge, precipitated wide QRS polymorphic ventricular tachycardia that resembled human torsades de pointes. Treatment with ATX-II produced similar effects at both the cellular level and in vivo. Importantly, nNav inhibition with riluzole or 4,9-anhydro-tetrodotoxin reduced the incidence of ATX-II\u2013, BayK-, or 4AP-induced EADs, DADs, aberrant Ca2+ release, and VT despite only modestly mitigating APD prolongation. These data reveal the contribution of nNaVs to triggered arrhythmias in murine models of LQT and CPVT-LQT overlap phenotypes. We also demonstrate the antiarrhythmic impact of nNaV inhibition, independent of action potential and QT interval duration, and provide a basis for a mechanistically driven antiarrhythmic strategy.<\/jats:p>","DOI":"10.1085\/jgp.201711909","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T11:25:20Z","timestamp":1527074720000},"page":"991-1002","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Tetrodotoxin-sensitive Navs contribute to early and delayed afterdepolarizations in long QT arrhythmia models"],"prefix":"10.1085","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9826-6442","authenticated-orcid":true,"given":"Megan","family":"Koleske","sequence":"first","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 1"},{"name":"Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6496-6387","authenticated-orcid":true,"given":"Justin","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Pharmacy Practice and Sciences, College of Pharmacy, The Ohio State University, Columbus, OH 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Zaman","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-4652","authenticated-orcid":true,"given":"Stephen","family":"Baine","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn C.","family":"Knollmann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Vanderbilt University Medical School, Nashville, TN 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8364-2222","authenticated-orcid":true,"given":"Rengasayee","family":"Veeraraghavan","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 1"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e1ndor","family":"Gy\u00f6rke","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 1"},{"name":"Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0750-2308","authenticated-orcid":true,"given":"Przemys\u0142aw B.","family":"Radwa\u0144ski","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 1"},{"name":"Division of Pharmacy Practice and Sciences, College of Pharmacy, The Ohio State University, Columbus, OH 3"},{"name":"Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,5,23]]},"reference":[{"key":"2023072705273568300_bib1","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1161\/CIRCRESAHA.110.224592","article-title":"Defining a new paradigm for human arrhythmia syndromes: Phenotypic manifestations of gene mutations in ion channel- and transporter-associated proteins","volume":"107","author":"Ackerman","year":"2010","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib2","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1093\/cvr\/cvt024","article-title":"\u2018Ryanopathy\u2019: Causes and manifestations of RyR2 dysfunction in heart failure","volume":"98","author":"Belevych","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"2023072705273568300_bib3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.yjmcc.2017.01.015","article-title":"The effect of PKA-mediated phosphorylation of ryanodine receptor on SR Ca2+ leak in ventricular myocytes","volume":"104","author":"Bovo","year":"2017","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023072705273568300_bib4","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1111\/j.1540-8167.2000.tb00342.x","article-title":"Block of I(Ks) does not induce early afterdepolarization activity but promotes beta-adrenergic agonist-induced delayed afterdepolarization activity","volume":"11","author":"Burashnikov","year":"2000","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"2023072705273568300_bib5","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/j.1540-8159.2006.00336.x","article-title":"Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation","volume":"29","author":"Burashnikov","year":"2006","journal-title":"Pacing Clin. Electrophysiol."},{"key":"2023072705273568300_bib6","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1161\/CIRCRESAHA.107.148064","article-title":"Arrhythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia","volume":"101","author":"Cerrone","year":"2007","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib7","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1161\/CIRCRESAHA.111.248252","article-title":"Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein","volume":"109","author":"Cheng","year":"2011","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib8","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12481","article-title":"Congenital long QT syndrome and torsade de pointes","author":"El-Sherif","year":"2017","journal-title":"Ann. Noninvasive Electrocardiol."},{"key":"2023072705273568300_bib9","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1161\/CIRCRESAHA.111.300076","article-title":"Accelerated sinus rhythm prevents catecholaminergic polymorphic ventricular tachycardia in mice and in patients","volume":"112","author":"Faggioni","year":"2013","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib10","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.cardiores.2007.06.019","article-title":"In vivo mechanisms precipitating torsades de pointes in a canine model of drug-induced long-QT1 syndrome","volume":"76","author":"Gallacher","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"2023072705273568300_bib11","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.hrthm.2008.09.013","article-title":"Molecular basis of catecholaminergic polymorphic ventricular tachycardia","volume":"6","author":"Gy\u00f6rke","year":"2009","journal-title":"Heart Rhythm."},{"key":"2023072705273568300_bib12","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.yjmcc.2006.12.005","article-title":"The promiscuous nature of the cardiac sodium current","volume":"42","author":"Haufe","year":"2007","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023072705273568300_bib13","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1161\/01.RES.62.3.563","article-title":"A model for early afterdepolarizations: Induction with the Ca2+ channel agonist Bay K 8644","volume":"62","author":"January","year":"1988","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib14","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1161\/01.RES.0000159387.00749.3c","article-title":"Cellular mechanism of calcium-mediated triggered activity in the heart","volume":"96","author":"Katra","year":"2005","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib15","first-page":"2510","article-title":"Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia","volume":"116","author":"Knollmann","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2023072705273568300_bib16","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.jacc.2010.09.064","article-title":"Systematic review of the incidence of sudden cardiac death in the United States","volume":"57","author":"Kong","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"2023072705273568300_bib17","doi-asserted-by":"publisher","first-page":"3267","DOI":"10.1113\/jphysiol.2010.187708","article-title":"Activation of reverse Na+-Ca2+ exchange by the Na+ current augments the cardiac Ca2+ transient: Evidence from NCX knockout mice","volume":"588","author":"Larbig","year":"2010","journal-title":"J. Physiol."},{"key":"2023072705273568300_bib18","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/j.hrthm.2011.07.016","article-title":"Subcellular heterogeneity of sodium current properties in adult cardiac ventricular myocytes","volume":"8","author":"Lin","year":"2011","journal-title":"Heart Rhythm."},{"key":"2023072705273568300_bib19","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1113\/jphysiol.1994.sp020035","article-title":"Sodium current-induced calcium signals in isolated guinea-pig ventricular myocytes","volume":"474","author":"Lipp","year":"1994","journal-title":"J. Physiol."},{"key":"2023072705273568300_bib20","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1093\/cvr\/cvs160","article-title":"Increased late sodium current contributes to long QT-related arrhythmia susceptibility in female mice","volume":"95","author":"Lowe","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"2023072705273568300_bib21","doi-asserted-by":"publisher","first-page":"4073","DOI":"10.1073\/pnas.261705699","article-title":"An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart","volume":"99","author":"Maier","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072705273568300_bib22","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1161\/01.CIR.0000121421.61896.24","article-title":"Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart","volume":"109","author":"Maier","year":"2004","journal-title":"Circulation."},{"key":"2023072705273568300_bib23","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1073\/pnas.1419992112","article-title":"A CaMKII\/PDE4D negative feedback regulates cAMP signaling","volume":"112","author":"Mika","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072705273568300_bib24","first-page":"H747","article-title":"Measurement of heart rate and Q-T interval in the conscious mouse","volume":"274","author":"Mitchell","year":"1998","journal-title":"Am. J. Physiol."},{"key":"2023072705273568300_bib25","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1136\/hrt.2005.078782","article-title":"Late sodium current in the pathophysiology of cardiovascular disease: Consequences of sodium-calcium overload","volume":"92","author":"Noble","year":"2006","journal-title":"Heart."},{"key":"2023072705273568300_bib26","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1096\/fj.10-179770","article-title":"A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation-contraction coupling in the mouse heart","volume":"26","author":"Noujaim","year":"2012","journal-title":"FASEB J."},{"key":"2023072705273568300_bib27","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1161\/01.CIR.103.2.196","article-title":"Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia","volume":"103","author":"Priori","year":"2001","journal-title":"Circulation."},{"key":"2023072705273568300_bib28","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1093\/cvr\/cvr180","article-title":"NCX is an important determinant for premature ventricular activity in a drug-induced model of Andersen-Tawil syndrome","volume":"92","author":"Radwa\u0144ski","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"2023072705273568300_bib29","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1016\/j.hrthm.2010.03.044","article-title":"Cytosolic calcium accumulation and delayed repolarization associated with ventricular arrhythmias in a guinea pig model of Andersen-Tawil syndrome","volume":"7","author":"Radwa\u0144ski","year":"2010","journal-title":"Heart Rhythm."},{"key":"2023072705273568300_bib30","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.hrthm.2012.10.005","article-title":"Inhibition of Na+ channels ameliorates arrhythmias in a drug-induced model of Andersen-Tawil syndrome","volume":"10","author":"Radwa\u0144ski","year":"2013","journal-title":"Heart Rhythm."},{"key":"2023072705273568300_bib31","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1093\/cvr\/cvu262","article-title":"Neuronal Na+ channel blockade suppresses arrhythmogenic diastolic Ca2+ release","volume":"106","author":"Radwa\u0144ski","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"2023072705273568300_bib32","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.jacbts.2016.04.004","article-title":"Neuronal Na+ channels are integral components of pro-arrhythmic Na+\/Ca2+ signaling nanodomain that promotes cardiac arrhythmias during \u03b2-adrenergic stimulation","volume":"1","author":"Radwa\u0144ski","year":"2016","journal-title":"JACC Basic Transl. Sci."},{"key":"2023072705273568300_bib33","doi-asserted-by":"publisher","first-page":"C783","DOI":"10.1152\/ajpcell.00070.2007","article-title":"The TTX metabolite 4,9-anhydro-TTX is a highly specific blocker of the Na(v1.6) voltage-dependent sodium channel","volume":"293","author":"Rosker","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2023072705273568300_bib34","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1161\/01.RES.87.10.910","article-title":"Distribution of a persistent sodium current across the ventricular wall in guinea pigs","volume":"87","author":"Sakmann","year":"2000","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib35","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/0014-2999(86)90369-9","article-title":"The positive chronotropic effects of Bay K-8644 and calcium as influenced by temperature","volume":"127","author":"Seifen","year":"1986","journal-title":"Eur. J. Pharmacol."},{"key":"2023072705273568300_bib36","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1093\/cvr\/cvs155","article-title":"Intracellular Ca2+ waves, afterdepolarizations, and triggered arrhythmias","volume":"95","author":"Shiferaw","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"2023072705273568300_bib37","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0022-3565(24)36856-9","article-title":"Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels","volume":"282","author":"Song","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2023072705273568300_bib38","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1161\/CIRCRESAHA.115.305146","article-title":"Hyperphosphorylation of RyRs underlies triggered activity in transgenic rabbit model of LQT2 syndrome","volume":"115","author":"Terentyev","year":"2014","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib39","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fphar.2011.00054","article-title":"Recent developments regarding voltage-gated sodium channel blockers for the treatment of inherited and acquired neuropathic pain syndromes","volume":"2","author":"Theile","year":"2011","journal-title":"Front. Pharmacol."},{"key":"2023072705273568300_bib40","doi-asserted-by":"publisher","first-page":"4249","DOI":"10.1113\/jphysiol.2010.194688","article-title":"Na+ currents are required for efficient excitation-contraction coupling in rabbit ventricular myocytes: A possible contribution of neuronal Na+ channels","volume":"588","author":"Torres","year":"2010","journal-title":"J. Physiol."},{"key":"2023072705273568300_bib41","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/j.1476-5381.2011.01367.x","article-title":"Cardiac ventricular repolarization reserve: A principle for understanding drug-related proarrhythmic risk","volume":"164","author":"Varr\u00f3","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"2023072705273568300_bib42","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1113\/JP273058","article-title":"Neuronal sodium channels: Emerging components of the nano-machinery of cardiac calcium cycling","volume":"595","author":"Veeraraghavan","year":"2017","journal-title":"J. Physiol."},{"key":"2023072705273568300_bib43","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.yjmcc.2014.09.009","article-title":"Intracellular Na+ overload causes oxidation of CaMKII and leads to Ca2+ mishandling in isolated ventricular myocytes","volume":"76","author":"Viatchenko-Karpinski","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023072705273568300_bib44","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/S0008-6363(96)00270-2","article-title":"Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes","volume":"34","author":"Volders","year":"1997","journal-title":"Cardiovasc. Res."},{"key":"2023072705273568300_bib45","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/S0008-6363(00)00022-5","article-title":"Progress in the understanding of cardiac early afterdepolarizations and torsades de pointes: Time to revise current concepts","volume":"46","author":"Volders","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"2023072705273568300_bib46","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1161\/01.RES.81.1.120","article-title":"Developmental changes in transient outward current in mouse ventricle","volume":"81","author":"Wang","year":"1997","journal-title":"Circ. Res."},{"key":"2023072705273568300_bib47","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/0092-8674(95)90359-3","article-title":"SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome","volume":"80","author":"Wang","year":"1995","journal-title":"Cell."},{"key":"2023072705273568300_bib48","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.yjmcc.2013.08.004","article-title":"Localization of sodium channel subtypes in mouse ventricular myocytes using quantitative immunocytochemistry","volume":"64","author":"Westenbroek","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023072705273568300_bib49","doi-asserted-by":"publisher","first-page":"H1553","DOI":"10.1152\/ajpheart.00459.2013","article-title":"Measurement and interpretation of electrocardiographic QT intervals in murine hearts","volume":"306","author":"Zhang","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/150\/7\/991\/1799301\/jgp_201711909.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/150\/7\/991\/1799301\/jgp_201711909.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T18:16:40Z","timestamp":1751653000000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/150\/7\/991\/43736\/Tetrodotoxin-sensitive-Navs-contribute-to-early"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,23]]},"references-count":49,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7,2]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.201711909","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,23]]}}}