{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:47:07Z","timestamp":1791085627307,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,6,18]]},"abstract":"<jats:p>\n                    Dysregulated intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling is implicated in a variety of cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia. Spontaneous diastolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release (DCR) can induce arrhythmogenic plasma membrane depolarizations, although the mechanism responsible for DCR synchronization among adjacent myocytes required for ectopic activity remains unclear. We investigated the synchronization mechanism(s) of DCR underlying untimely action potentials and diastolic contractions (DCs) in a catecholaminergic polymorphic ventricular tachycardia mouse model with a mutation in cardiac calsequestrin. We used a combination of different approaches including single ryanodine receptor channel recording, optical imaging (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and membrane potential), and contractile force measurements in ventricular myocytes and intact cardiac muscles. We demonstrate that DCR occurs in a temporally and spatially uniform manner in both myocytes and intact myocardial tissue isolated from cardiac calsequestrin mutation mice. Such synchronized DCR events give rise to triggered electrical activity that results in synchronous DCs in the myocardium. Importantly, we establish that synchronization of DCR is a result of a combination of abbreviated ryanodine receptor channel refractoriness and the preceding synchronous stimulated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release\/reuptake dynamics. Our study reveals how aberrant DCR events can become synchronized in the intact myocardium, leading to triggered activity and the resultant DCs in the settings of a cardiac rhythm disorder.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1300052110","type":"journal-article","created":{"date-parts":[[2013,6,4]],"date-time":"2013-06-04T01:42:51Z","timestamp":1370310171000},"page":"10312-10317","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":53,"title":["Decreased RyR2 refractoriness determines myocardial synchronization of aberrant Ca\n                    <sup>2+<\/sup>\n                    release in a genetic model of arrhythmia"],"prefix":"10.1073","volume":"110","author":[{"given":"Lucia","family":"Brunello","sequence":"first","affiliation":[{"name":"D. Davis Heart and Lung Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Slabaugh","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142aw B.","family":"Radwa\u0144ski","sequence":"additional","affiliation":[{"name":"D. Davis Heart and Lung Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Ting","family":"Ho","sequence":"additional","affiliation":[{"name":"D. Davis Heart and Lung Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy E.","family":"Belevych","sequence":"additional","affiliation":[{"name":"D. Davis Heart and Lung Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Lou","sequence":"additional","affiliation":[{"name":"D. Davis Heart and Lung Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Physiology, Section of Cellular Signaling, Rush University Medical Center, Chicago, IL 60612;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Divisione di Cardiologia, Instituto di Ricovero e Cura a Carattere Scientifico Fondazione Salvatore Maugeri, 27100 Pavia, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Lodola","sequence":"additional","affiliation":[{"name":"Divisione di Cardiologia, Instituto di Ricovero e Cura a Carattere Scientifico Fondazione Salvatore Maugeri, 27100 Pavia, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia G.","family":"Priori","sequence":"additional","affiliation":[{"name":"Divisione di Cardiologia, Instituto di Ricovero e Cura a Carattere Scientifico Fondazione Salvatore Maugeri, 27100 Pavia, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim V.","family":"Fedorov","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pompeo","family":"Volpe","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fill","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Physiology, Section of Cellular Signaling, Rush University Medical Center, Chicago, IL 60612;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M. 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