scholarly journals Role of CaMKII and PKA in Early Afterdepolarization of Human Ventricular Myocardium Cell: A Computational Model Study

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ling Dai ◽  
Yunliang Zang ◽  
Dingchang Zheng ◽  
Ling Xia ◽  
Yinglan Gong
Keyword(s):  
Computational Model ◽  
Signaling Pathway ◽  
Experimental Studies ◽  
Ventricular Myocardium ◽  
Delayed Rectifier ◽  
Adrenergic Signaling ◽  
Model Study ◽  
Early Afterdepolarization ◽  
Human Ventricular Myocardium

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 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 and β-adrenergic signaling pathway on the occurrence of EADs, which could be useful for searching for therapy strategies to treat EADs related arrhythmogenesis.

The Role of Silanols in the Interactions between Methyltert-Butyl Ether and High-Silica Faujasite Y: An Infrared Spectroscopy and Computational Model Study

2012 ◽  
Vol 116 (12) ◽  
pp. 6943-6952 ◽  
Author(s):  
Ilaria Braschi ◽  
Giorgio Gatti ◽  
Chiara Bisio ◽  
Gloria Berlier ◽  
Vittoria Sacchetto ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Computational Model ◽  
Butyl Ether ◽  
Model Study ◽  
High Silica

scholarly journals Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium.

1990 ◽  
Vol 85 (5) ◽  
pp. 1599-1613 ◽  
Author(s):  
J K Gwathmey ◽  
M T Slawsky ◽  
R J Hajjar ◽  
G M Briggs ◽  
J P Morgan
Keyword(s):  
Intracellular Calcium ◽  
Ventricular Myocardium ◽  
Calcium Handling ◽  
Human Ventricular Myocardium

A model study of changes in excitability of ventricular muscle cells: inhibition, facilitation, and hysteresis

1995 ◽  
Vol 268 (3) ◽  
pp. H1181-H1194 ◽  
Author(s):  
J. Beaumont ◽  
D. C. Michaels ◽  
M. Delmar ◽  
J. Davidenko ◽  
J. Jalife
Keyword(s):  
Experimental Studies ◽  
Inward Rectifier ◽  
Delayed Rectifier ◽  
Passive Component ◽  
Ventricular Muscle ◽  
Membrane Excitability ◽  
Ionic Model ◽  
Long Cycle ◽  
Model Study ◽  
Cycle Lengths

A model study was carried out to investigate the mechanism of changes in excitability at long cycle lengths (i.e., > 1,000 ms), which are responsible for various phenomena, including electrotonic inhibition, active facilitation, and hysteresis of excitability in ventricular muscle at slow frequencies of stimulation. Experimental studies suggested that with repetitive activity the inward rectifier potassium current (IK1) is not a passive component of membrane response and that the dynamics of IK1 are responsible for the changes in excitability at long cycle lengths. In the present study, we have used new experimental data as the basis to modify the equations for IK1 in the ionic model for ventricular muscle of the Luo and Rudy (LR) model. The modified equations for IK1 incorporate an additional slow gate (s-gate), which governs the transition from a high steady-state conductance at rest to a lower conductance with repetitive stimulation. In simulation studies, electronic inhibition was seen in the original and the modified LR model and was shown to depend on changes in the delayed rectifier current (IK). However, addition of the s-gate to IK1 of the LR model extended the frequency dependence of excitability to longer cycle lengths and allowed for the demonstration of active facilitation and hysteresis. These results support the hypothesis that the inward rectifier is involved in the dynamic control of membrane excitability. The overall results provide mechanistic explanations for heart rate-dependent excitation abnormalities that may be involved in the genesis of cardiac arrhythmias.

scholarly journals Transcriptional analysis of lung epithelial cells using WGCNA revealed the role of IRF9 and IFI6 genes in SARS-CoV-2 pathogenicity

2020 ◽  
Author(s):  
Hassan Karami ◽  
Afshin Derakhshani ◽  
Mohammad Fereidouni ◽  
Ebrahim Miri-Moghaddam ◽  
Behzad Baradaran ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Experimental Studies ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Transcriptional Analysis ◽  
Type I ◽  
Hub Genes

Abstract The coronavirus disease 2019 (COVID-19) outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. Here, we applied weighted gene co-expression network analysis to comprehensively characterize transcriptional changes in bronchial epithelium cells (NHBE and A549 cells) during SARS-CoV-2 infection. Our analysis identified a network highly correlated to COVID-19 pathogenicity based on MX1, IFIT1, ISG15, IFI6, DDX60, IRF9, PARP9, PGLYRP4, IL36G, SAA2 and IL-8 hub genes. The results also indicated a unique transcriptional signatures of infected cells including IFI6 and IRF9 as novel gene candidates and suggested their prospective mechanism in COVID-19 pathogenesis. The result of hub genes enrichment showed that the most correlation topic in biological process and KEGG were type I interferon signaling pathway, IL-17 signaling pathway, cytokine mediated signaling pathway, and defense response to virus categories which all play significant roles in restricting viral infection. Also according to the drug-target network, we recognized 54 FDA-approved drug candidates for other indications could potentially use for the treatment of COVID-19 patients through regulation of six hub genes of the co-expression network. Our findings also showed that the 19 experimentally validated miRNAs regulated the co-expression network through 5 hub genes (SLC19A3, FAM13A, PLA2G16, and HRASLS5). In conclusion, these hub genes had potential roles in the translational medicine and might become promising therapeutic targets further in vitro and in vivo experimental studies are needed to evaluate the role of above mentioned genes in COVID-19.

285: The Role of the NF-κB Signaling Pathway in the Pathogenesis of Interstitial Cystitis

2006 ◽  
Vol 175 (4S) ◽  
pp. 95-95
Author(s):  
Raymond R. Rackley ◽  
Mei Kuang ◽  
Ashwin A. Vaze ◽  
Joseph Abdelmalak ◽  
Sandip P. Vasavada ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Signaling Pathway
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