ArticleJournal of molecular and cellular cardiology2012
Phospholemman is a negative feed-forward regulator of Ca2+ in β-adrenergic signaling, accelerating β-adrenergic inotropy.
Article in Journal of molecular and cellular cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- 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
- Review
- Quantitative cross-species translators of cardiac myocyte electrophysiology: Model training, experimental validation, and applications.Science advances · 2021Article
- Quantitative analysis of variability in an integrated model of human ventricular electrophysiology and β-adrenergic signaling.Journal of molecular and cellular cardiology · 2020Article
- A Mathematical Model of the Mouse Atrial Myocyte With Inter-Atrial Electrophysiological Heterogeneity.Frontiers in physiology · 2020Article
- Different paths, same destination: divergent action potential responses produce conserved cardiac fight-or-flight response in mouse and rabbit hearts.The Journal of physiology · 2019Article
- Mechanisms of the cyclic nucleotide cross-talk signaling network in cardiac L-type calcium channel regulation.Journal of molecular and cellular cardiology · 2017Article
- Over-expression of microRNA-1 causes arrhythmia by disturbing intracellular trafficking system.Scientific reports · 2017Article
- Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention.Annals of biomedical engineering · 2016Article
- In silico prediction of drug therapy in catecholaminergic polymorphic ventricular tachycardia.The Journal of physiology · 2016Article
- Interaction between phosphodiesterases in the regulation of the cardiac β-adrenergic pathway.Journal of molecular and cellular cardiology · 2015Article
- β-adrenergic effects on cardiac myofilaments and contraction in an integrated rabbit ventricular myocyte model.Journal of molecular and cellular cardiology · 2015Article
- Bridging scales through multiscale modeling: a case study on protein kinase A.Frontiers in physiology · 2015Review
- Arrhythmogenic transient dynamics in cardiac myocytes.Biophysical journal · 2014Article
- A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII.The Journal of physiology · 2014Article
- A compartmentalized mathematical model of the β1-adrenergic signaling system in mouse ventricular myocytes.PloS one · 2014Article
- PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling.Journal of molecular and cellular cardiology · 2014Article
- β-adrenergic stimulation activates early afterdepolarizations transiently via kinetic mismatch of PKA targets.Journal of molecular and cellular cardiology · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Sympathetic stimulation enhances cardiac contractility by stimulating β-adrenergic signaling and protein kinase A (PKA). Recently, phospholemman (PLM) has emerged as an important PKA substrate capable of regulating cytosolic Ca(2+) transients. However, it remains unclear how PLM contributes to β-adrenergic inotropy. Here we developed a computational model to clarify PLM's role in the β-adrenergic signaling response. Simulating Na(+) and sarcoplasmic reticulum (SR) Ca(2+) clamps, we identify an effect of PLM phosphorylation on SR unloading as the key mechanism by which PLM confers cytosolic Ca(2+) adaptation to long-term β-adrenergic receptor (β-AR) stimulation. Moreover, we show that phospholamban (PLB) opposes and overtakes these actions on SR load, forming a negative feed-forward loop in the β-adrenergic signaling cascade. This network motif dominates the negative feedback conferred by β-AR desensitization and accelerates β-AR-induced inotropy. Model analysis therefore unmasks key actions of PLM phosphorylation during β-adrenergic signaling, indicating that PLM is a critical component of the fight-or-flight response.
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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.