title: Role of CaMKII and PKA in Early Afterdepolarization of Human Ventricular Myocardium Cell: A Computational Model Study.
abstract: Early afterdepolarization (EAD) plays an important role in arrhythmogenesis. Many experimental studies have reported that Ca2+/calmodulin-dependent protein kinase II (CaMKII) andβ-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 andβ-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 ofβ-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 (IKr) blockage (77% versus 85%). In summary, this study computationally demonstrated the combined role of CaMKII andβ-adrenergic signaling pathway on the occurrence of EADs, which could be useful for searching for therapy strategies to treat EADs related arrhythmogenesis.
authors.affiliation: Department of Biomedical Engineering, Zhejiang University, Hangzhou, China.
authors.forename: Ling
authors.identifier: 0000-0002-6839-2923
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department of Biomedical Engineering, Zhejiang University, Hangzhou, China.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Zang
authors.affiliation: Health and Wellbeing Academy, Faculty of Medical Science, Anglia Ruskin University, Chelmsford CM1 1SQ, UK.
authors.forename: Dingchang
authors.identifier: 0000-0001-8077-4548
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Biomedical Engineering, Zhejiang University, Hangzhou, China.
authors.forename: Ling
authors.identifier: 0000-0002-1937-9693
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Biomedical Engineering, Zhejiang University, Hangzhou, China.
authors.forename: Yinglan
authors.identifier: 0000-0003-1533-1446
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D003198:Computer Simulation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004285:Dogs; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008955:Models, Cardiovascular; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D015221:Potassium Channels / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium