{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:11:42Z","timestamp":1779196302072,"version":"3.51.4"},"reference-count":47,"publisher":"American Society for Clinical Investigation","issue":"22","funder":[{"name":"NIH","award":["P01 HL78931,R56 HL71140,R42DA043391,TR002208-01,R01 HL139829"],"award-info":[{"award-number":["P01 HL78931,R56 HL71140,R42DA043391,TR002208-01,R01 HL139829"]}]},{"name":"Krannert Institute of Cardiology, Indiana University","award":["29-827-11 MCHEN"],"award-info":[{"award-number":["29-827-11 MCHEN"]}]},{"name":"Indiana University Health-Indiana Univerjsity School of Medicine Strategic Research Initiative","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Medtronic-Zipes Endowment","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P01 HL78931,R56 HL71140,R42DA043391,TR002208-01,R01 HL139829"],"award-info":[{"award-number":["P01 HL78931,R56 HL71140,R42DA043391,TR002208-01,R01 HL139829"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,15]]},"abstract":"<jats:p>\n                    The mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>KAS<\/jats:sub>\n                    ) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay.\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>KAS<\/jats:sub>\n                    activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>Na<\/jats:sub>\n                    ) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>KAS<\/jats:sub>\n                    blockade by apamin reduced J wave elevation and eliminated SVF. \u03b2-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0\u00b0C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>KAS<\/jats:sub>\n                    activation contributes to the development of JWS in rabbit ventricles.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.122329","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T11:01:38Z","timestamp":1542193298000},"source":"Crossref","is-referenced-by-count":19,"title":["Concomitant SK current activation and sodium current inhibition cause J wave syndrome"],"prefix":"10.1172","volume":"3","author":[{"given":"Mu","family":"Chen","sequence":"first","affiliation":[{"name":"Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Zhu","family":"Xu","sequence":"additional","affiliation":[{"name":"Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Cardiovascular Division, Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adonis Z.","family":"Wu","sequence":"additional","affiliation":[{"name":"Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Guo","sequence":"additional","affiliation":[{"name":"Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1314-1673","authenticated-orcid":true,"given":"Juyi","family":"Wan","sequence":"additional","affiliation":[{"name":"Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Department of Cardiothoracic Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dechun","family":"Yin","sequence":"additional","affiliation":[{"name":"Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA."},{"name":"Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 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