ArticleJournal of molecular and cellular cardiology2011
Local control of β-adrenergic stimulation: Effects on ventricular myocyte electrophysiology and Ca(2+)-transient.
Article in Journal of molecular and cellular cardiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 141 citations in OpenAlex.
- The β1 adrenoceptor (AR) blocker metoprolol normalises βAR cascade and caveolar protein expression and restores β1AR responsiveness in failing right ventricular myocytes.Journal of molecular and cellular cardiology plus · 2026Article
- Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation.The Journal of physiology · 2026Review
- T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.Circulation research · 2026Article
- A model of β-adrenergic stimulation in human ventricular cells for tissue-scale simulations of sympathetically modulated tachycardias.The Journal of physiology · 2026Article
- Interplay between variability in intrinsic cellular properties and heart failure-associated remodeling in a simulated population with human heart failure.Journal of molecular and cellular cardiology · 2026Article
- Computational modelling for improved translation of cardiac inotropic and lusitropic drug effects from rats to humans.Journal of pharmacological and toxicological methods · 2025Article
- T-World: A highly general computational model of a human ventricular myocyte.bioRxiv : the preprint server for biology · 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
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- CNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2.Circulation research · 2023Article
- Models of the cardiac L-type calcium current: A quantitative review.WIREs mechanisms of disease · 2023Review
- Pro-arrhythmic role of adrenergic spatial densities in the human atria: An in-silico study.PloS one · 2023Article
- The role of β-adrenergic stimulation in QT interval adaptation to heart rate during stress test.PloS one · 2023Article
- Nanoscale organization of ryanodine receptor distribution and phosphorylation pattern determines the dynamics of calcium sparks.PLoS computational biology · 2022Article
- Paradoxical prolongation of QT interval during exercise in patients with hypertrophic cardiomyopathy: cellular mechanisms and implications for diastolic function.European heart journal open · 2022Article
- Article
- Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.Biomolecules · 2022Review
- Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.Frontiers in physiology · 2022Review
- Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression.International journal of molecular sciences · 2021Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Local signaling domains and numerous interacting molecular pathways and substrates contribute to the whole-cell response of myocytes during β-adrenergic stimulation (βARS). We aimed to elucidate the quantitative contribution of substrates and their local signaling environments during βARS to the canine epicardial ventricular myocyte electrophysiology and calcium transient (CaT). We present a computational compartmental model of βARS and its electrophysiological effects. Novel aspects of the model include localized signaling domains, incorporation of β1 and β2 receptor isoforms, a detailed population-based approach to integrate the βAR and Ca(2+)/Calmodulin kinase (CaMKII) signaling pathways and their effects on a wide range of substrates that affect whole-cell electrophysiology and CaT. The model identifies major roles for phosphodiesterases, adenylyl cyclases, PKA and restricted diffusion in the control of local cAMP levels and shows that activation of specific cAMP domains by different receptor isoforms allows for specific control of action potential and CaT properties. In addition, the model predicts increased CaMKII activity during βARS due to rate-dependent accumulation and increased Ca(2+) cycling. CaMKII inhibition, reduced compartmentation, and selective blockade of β1AR is predicted to reduce the occurrence of delayed afterdepolarizations during βARS. Finally, the relative contribution of each PKA substrate to whole-cell electrophysiology is quantified by comparing simulations with and without phosphorylation of each target. In conclusion, this model enhances our understanding of localized βAR signaling and its whole-cell effects in ventricular myocytes by incorporating receptor isoforms, multiple pathways and a detailed representation of multiple-target phosphorylation; it provides a basis for further studies of βARS under pathological conditions.
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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.