ArticleBiophysical journal2010
Synergy between CaMKII substrates and β-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 121 citations in OpenAlex.
- Istaroxime in Acute Heart Failure and Early Cardiogenic Shock: A Calcium-Cycling Approach to Inotropic Therapy.International journal of molecular sciences · 2026Review
- T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.Circulation research · 2026Article
- Metabolic-Electrophysiological Coupling in Heart Failure: from Bidirectional Decoupling to Therapeutic Recoupling.Current heart failure reports · 2025Review
- Positive feedback between RyR phosphorylation and CaBiophysical journal · 2025Article
- Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes.iScience · 2025Article
- Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.Physiological reviews · 2024Review
- Computational Modeling of Cardiac Electrophysiology.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis.Cardiovascular research · 2023Article
- A multiscale predictive digital twin for neurocardiac modulation.The Journal of physiology · 2023Article
- The promise of cardiac neuromodulation: can computational modelling bridge the gap?The Journal of physiology · 2023Article
- Lysosomal calcium loading promotes spontaneous calcium release by potentiating ryanodine receptors.Biophysical journal · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Pro-arrhythmic role of adrenergic spatial densities in the human atria: An in-silico study.PloS one · 2023Article
- Models of the cardiac L-type calcium current: A quantitative review.WIREs mechanisms of disease · 2023Review
- Mutation-Specific Differences in Kv7.1 (International journal of molecular sciences · 2022Review
- Quantitative cross-species translators of cardiac myocyte electrophysiology: Model training, experimental validation, and applications.Science advances · 2021Article
- Extracorporeal Shock Wave Enhanced Exogenous Mitochondria into Adipose-Derived Mesenchymal Stem Cells and Further Preserved Heart Function in Rat Dilated Cardiomyopathy.Biomedicines · 2021Article
- Molecular noise filtering in the β-adrenergic signaling network by phospholamban pentamers.Cell reports · 2021Article
- Dynamics of adrenergic signaling in cardiac myocytes and implications for pharmacological treatment.Journal of theoretical biology · 2021Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac excitation-contraction coupling is a highly coordinated process that is controlled by protein kinase signaling pathways, including Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA). Increased CaMKII expression and activity (as occurs during heart failure) destabilizes EC coupling and may lead to sudden cardiac death. To better understand mechanisms of cardiac CaMKII function, we integrated dynamic CaMKII-dependent regulation of key Ca(2+) handling targets with previously validated models of cardiac EC coupling, Ca(2+)/calmodulin-dependent activation of CaMKII, and β-adrenergic activation of PKA. Model predictions are validated against CaMKII-overexpression data from rabbit ventricular myocytes. The model demonstrates how overall changes to Ca(2+) handling during CaMKII overexpression are explained by interactions between individual CaMKII substrates. CaMKII and PKA activities during β-adrenergic stimulation may synergistically facilitate inotropic responses and contribute to a CaMKII-Ca(2+)-CaMKII feedback loop. CaMKII regulated early frequency-dependent acceleration of relaxation and EC coupling gain (which was highly sarcoplasmic reticulum Ca(2+) load-dependent). Additionally, the model identifies CaMKII-dependent ryanodine receptor hyperphosphorylation as a proarrhythmogenic trigger. In summary, we developed a detailed computational model of CaMKII and PKA signaling in cardiac myocytes that provides unique insights into their regulation of normal and pathological Ca(2+) handling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.