{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T15:46:57Z","timestamp":1758815217011,"version":"3.41.0"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61527811"],"award-info":[{"award-number":["61527811"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computational and Mathematical Methods in Medicine"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>Early afterdepolarization (EAD) plays an important role in arrhythmogenesis. Many experimental studies have reported that Ca<jats:sup>2+<\/jats:sup>\/calmodulin-dependent protein kinase II (CaMKII) and<jats:italic>\u03b2<\/jats:italic>-adrenergic signaling pathway are two important regulators. In this study, we developed a modified computational model of human ventricular myocyte to investigate the combined role of CaMKII and<jats:italic>\u03b2<\/jats:italic>-adrenergic signaling pathway on the occurrence of EADs. Our simulation results showed that (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mn fontstyle=\"italic\">1<\/mml:mn><\/mml:mrow><\/mml:math>) CaMKII overexpression facilitates EADs through the prolongation of late sodium current\u2019s (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:msub><mml:mrow><mml:mi>I<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi mathvariant=\"normal\">N<\/mml:mi><mml:mi mathvariant=\"normal\">a<\/mml:mi><mml:mi mathvariant=\"normal\">L<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>) deactivation progress; (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:mn fontstyle=\"italic\">2<\/mml:mn><\/mml:mrow><\/mml:math>) the combined effect of CaMKII overexpression and activation of<jats:italic>\u03b2<\/jats:italic>-adrenergic signaling pathway further increases the risk of EADs, where EADs could occur at shorter cycle length (2000\u2009ms versus 4000\u2009ms) and lower rapid delayed rectifier K<jats:sup>+<\/jats:sup>current (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mrow><mml:msub><mml:mrow><mml:mi>I<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi mathvariant=\"normal\">K<\/mml:mi><mml:mi mathvariant=\"normal\">r<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>) blockage (77% versus 85%). In summary, this study computationally demonstrated the combined role of CaMKII and<jats:italic>\u03b2<\/jats:italic>-adrenergic signaling pathway on the occurrence of EADs, which could be useful for searching for therapy strategies to treat EADs related arrhythmogenesis.<\/jats:p>","DOI":"10.1155\/2016\/4576313","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T21:01:12Z","timestamp":1481230872000},"page":"1-8","source":"Crossref","is-referenced-by-count":11,"title":["Role of CaMKII and PKA in Early Afterdepolarization of Human Ventricular Myocardium Cell: A Computational Model Study"],"prefix":"10.1155","volume":"2016","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6839-2923","authenticated-orcid":true,"given":"Ling","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Zhejiang University, Hangzhou, 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