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 () CaMKII overexpression facilitates EADs through the prolongation of late sodium current’s () deactivation progress; () 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 versus 4000 ms) and lower rapid delayed rectifier K+ current () blockage (77% versus 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 for therapy strategies to treat EADs related arrhythmogenesis.
|Number of pages||8|
|Journal||Computational and Mathematical Methods in Medicine|
|Publication status||Published - 8 Dec 2016|
Bibliographical noteThis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Dai, L., Zang, Y., Zheng, D., Xia, L., & Gong, Y. (2016). Role of CaMKII and PKA in Early Afterdepolarization of Human Ventricular Myocardium Cell: A Computational Model Study. Computational and Mathematical Methods in Medicine, 2016, [4576313 ]. https://doi.org/10.1155/2016/4576313