Role of CaMKII and PKA in early afterdepolarization of human ventricular myocardium cell: A Computational model study
journal contributionposted on 2023-07-26, 14:01 authored by Ling Dai, Zang Yunliang, Dingchang Zheng, Xia Ling
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.
Publication titleComputational and Mathematical Methods in Medicine
- Published version