Role of CaMKII and PKA in early afterdepolarization of human ventricular myocardium cell: A Computational model study

Dai, Ling and Yunliang, Zang and Zheng, Dingchang and Ling, Xia (2016) Role of CaMKII and PKA in early afterdepolarization of human ventricular myocardium cell: A Computational model study. Computational and Mathematical Methods in Medicine.

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Official URL: http://dx.doi.org/10.1155/2016/4576313

Abstract

Early afterdepolarization (EAD) plays an important role in arrhythmogenesis. Many experimental studies have reported that Ca2+/Calmodulin-dependent protein kinase II (CaMKII) and β-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 β-adrenergic signaling pathway on the occurrence of EADs. Our simulation results showed that 1) CaMKII overexpression facilitates EADs through the prolongation of late sodium current’s (INaL) deactivation progress; 2) the combined effect of CaMKII overexpression and activation of β-adrenergic signaling pathway further increases the risk of EADs, where EADs could occur at shorter cycle length (2000 ms vs 4000 ms) and lower rapid delayed rectifier K+ current (IKr) blockage (77% vs 85%). In summary, this study computationally demonstrated the combined role of CaMKII and β-adrenergic signaling pathway on the occurrence of EADs, which could be useful for searching therapy strategies to treat EADs related arrhythmogenesis

Item Type: Journal Article
Keywords: Early afterdepolarization, Human ventricular, Computational model
Faculty: Faculty of Medical Science
Depositing User: Dr D Zheng
Date Deposited: 12 Dec 2016 14:13
Last Modified: 12 Dec 2016 14:13
URI: http://arro.anglia.ac.uk/id/eprint/701295

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