ReviewCirculation research2014
Role of RyR2 phosphorylation in heart failure and arrhythmias: protein kinase A-mediated hyperphosphorylation of the ryanodine receptor at serine 2808 does not alter cardiac contractility or cause heart failure and arrhythmias.
Review in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- Ryanodine receptor 2 mutations in catecholaminergic polymorphic ventricular tachycardia: From molecular mechanisms to precision medicine.World journal of cardiology · 2026Review
- Finding the right balance of RyR2 phosphorylation for arrhythmia prevention.Nature cardiovascular research · 2025Article
- Preventing the phosphorylation of RyR2 at canonical sites reduces CaNature cardiovascular research · 2025Article
- Inhibition of the upregulated phosphodiesterase 4D isoforms improves SERCA2a function in diabetic cardiomyopathy.British journal of pharmacology · 2025Article
- Nsun2 controls cardiac homeostasis and hypertrophic response by regulating PRKACA expression.Theranostics · 2025Article
- Single-cell transcriptional profiling of hearts during cardiac hypertrophy reveals the role of MAMs in cardiomyocyte subtype switching.Scientific reports · 2023Article
- Changes in cellular CaThe Journal of physiology · 2023Article
- Increased β1-adrenergic receptor antibody confers a vulnerable substrate for atrial fibrillation via mediating Ca2+ mishandling and atrial fibrosis in active immunization rabbit models.Clinical science (London, England : 1979) · 2023Article
- Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics.Open medicine (Warsaw, Poland) · 2023Article
- Function and regulation of ubiquitin-like SUMO system in heart.Frontiers in cell and developmental biology · 2023Review
- Review
- Physiological and pathological roles of protein kinase A in the heart.Cardiovascular research · 2022Review
- Proteome-wide profiling and mapping of post translational modifications in human hearts.Scientific reports · 2021Article
- Endoplasmic Reticulum Stress/CaFrontiers in physiology · 2021Article
- RyR2 and Calcium Release in Heart Failure.Frontiers in physiology · 2021Review
- Multisite phosphorylation of the cardiac ryanodine receptor: a random or coordinated event?Pflugers Archiv : European journal of physiology · 2020Review
- Deletion of cardiac polycystin 2/PC2 results in increased SR calcium release and blunted adrenergic reserve.American journal of physiology. Heart and circulatory physiology · 2020Article
- Loss of SPEG Inhibitory Phosphorylation of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation.Circulation · 2020Article
- Nkx2.5 insufficiency leads to atrial electrical remodeling through Wnt signaling in HL-1 cells.Experimental and therapeutic medicine · 2019Article
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1 author at 1 institution in 1 country.
Funding
Abstract
This Controversies in Research article discusses the hypothesis that protein kinase A (PKA)-mediated phosphorylation of the Ryanodine Receptor (RyR) at a single serine (RyRS2808) is essential for normal sympathetic regulation of cardiac myocyte contractility and is responsible for the disturbed Ca(2+) regulation that underlies depressed contractility in heart failure. Studies supporting this hypothesis have associated hyperphosphorylation of RyRS2808 and heart failure progression in animals and humans and have shown that a phosphorylation defective RyR mutant mouse (RyRS2808A) does not respond normally to sympathetic agonists and does not exhibit heart failure symptoms after myocardial infarction. Studies to confirm and extend these ideas have failed to support the original data. Experiments from many different laboratories have convincingly shown that PKA-mediated RyRS2808 phosphorylation does not play any significant role in the normal sympathetic regulation of sarcoplasmic reticulum Ca2+ release or cardiac contractility. Hearts and myocytes from RyRS2808A mice have been shown to respond normally to sympathetic agonists, and to increase Ca(2+) influx, Ca(2+) transients, and Ca(2+) efflux. Although the RyR is involved in heart failure-related Ca(2+) disturbances, this results from Ca(2+)-calmodulin kinase II and reactive oxygen species-mediated regulation rather than by RyR2808 phosphorylation. Also, a new study has shown that RyRS2808A mice are not protected from myocardial infarction. Collectively, there is now a clear consensus in the published literature showing that dysregulated RyRs contribute to the altered Ca(2+) regulatory phenotype of the failing heart, but PKA-mediated phosphorylation of RyRS2808 has little or no role in these alterations.
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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.