{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:34:35Z","timestamp":1791686075467,"version":"4.3.4"},"reference-count":95,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015891","name":"AHA","doi-asserted-by":"publisher","award":["23POST1027462"],"award-info":[{"award-number":["23POST1027462"]}],"id":[{"id":"10.13039\/501100015891","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["1R01GM099490"],"award-info":[{"award-number":["1R01GM099490"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In Duchenne muscular dystrophy (DMD), connexin-43 (Cx43) delocalizes from intercalated discs to the lateral membrane of cardiomyocytes, where it forms undocked hemichannels. \u03b2-adrenergic stress induces lethal arrhythmias in DMDmdx mice that correlate with increased Cx43 S-nitrosylation and excessive hemichannel opening. Here, we aimed to determine whether S-nitrosylation of Cx43 at cysteine 271 directly contributes to \u03b2-adrenergic stress\u2013induced arrhythmias and myocardial injury in DMD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>To define the role of Cx43 S-nitrosylation in DMD cardiomyopathy, we generated DMDmdx knock-in mice carrying a cysteine-to-serine substitution at residue 271, a critical S-nitrosylation site involved in NO-dependent Cx43 hemichannel activation (DMDmdx:C271S+\/\u2212). Following \u03b2-adrenergic stimulation, DMDmdx mice exhibited a higher incidence of arrhythmogenic events and increased triggered activity in isolated cardiomyocytes compared with DMDmdx:C271S+\/\u2212 mice, which more closely resembled wild-type mice. Optical mapping of isolated hearts showed that DMDmdx mice developed abnormal Ca2+ transients, prolonged action potentials, and episodes of conduction block. These abnormalities were normalized in DMDmdx:C271S+\/\u2212 mice and attenuated by treatment with the Cx43 hemichannel inhibitor Gap19. Moreover, \u03b2-adrenergic stress evoked severe myocardial injury and bradycardia in DMDmdx mice, both of which were significantly attenuated in DMDmdx:C271S+\/\u2212 mice. Notably, Gap19-treated DMDmdx mice were protected against myocardial injury, further supporting a direct role for Cx43 hemichannels in DMD-associated cardiac damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings reveal, for the first time, a mechanistic link between Cx43 hemichannel activity, arrhythmogenesis, and myocardial injury in DMD. We conclude that S-nitrosylation of Cx43 is a fundamental NO-mediated mechanism driving \u03b2-adrenergic stress\u2013induced arrhythmias and myocardial injury in DMDmdx mice through pathological opening of Cx43 hemichannels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag170","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:11:47Z","timestamp":1786101107000},"page":"1947-1963","source":"Crossref","is-referenced-by-count":0,"title":["Reduced Cx43 S-nitrosylation protects against cardiac stress\u2013induced arrhythmias and myocardial injury in Duchenne muscular dystrophy"],"prefix":"10.1093","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-9600","authenticated-orcid":false,"given":"Manuel F","family":"Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Department of Physiology and Membrane Biology, University of California , One Shields Avenue, Davis, CA 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo S","family":"Gaete","sequence":"additional","affiliation":[{"name":"Department of Physiology and Membrane Biology, University of California , One Shields Avenue, Davis, CA 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Membrane Biology, University of California , One Shields Avenue, Davis, CA 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao T","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Membrane Biology, University of California , One Shields Avenue, Davis, CA 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Nuno","sequence":"additional","affiliation":[{"name":"Department of Physiology and Membrane Biology, University of California , One Shields Avenue, Davis, CA 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4794-9285","authenticated-orcid":false,"given":"Adrian","family":"Sheehy","sequence":"additional","affiliation":[{"name":"Department of Physiology and Membrane Biology, University of California , One Shields Avenue, Davis, CA 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila A","family":"Araujo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Membrane Biology, University of California , One Shields Avenue, Davis, CA 95616 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4331-3336","authenticated-orcid":false,"given":"Pia C","family":"Burboa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Neuroscience, Rutgers University, New Jersey Medical School , Newark, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-6619","authenticated-orcid":false,"given":"Mauricio A","family":"Lillo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Neuroscience, Rutgers University, New Jersey Medical School , Newark, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9203-1602","authenticated-orcid":false,"given":"Jorge E","family":"Contreras","sequence":"additional","affiliation":[{"name":"Department of Physiology and Membrane Biology, University of California , One Shields Avenue, Davis, CA 95616 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