ArticleProceedings of the National Academy of Sciences of the United States of America2006
Ryanodine receptor/calcium release channel PKA phosphorylation: a critical mediator of heart failure progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers.
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Who cites it
194 citing papers in PubMed, 364 citations in OpenAlex.
- Trial
- Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial.Diabetes, obesity & metabolism · 2023 · on this mapTrial
- Ryanodine receptor cluster remodeling linksbioRxiv : the preprint server for biology · 2026Article
- βNaunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Structural and Functional Regulation of RyR2 in Cardiac Calcium Handling and Arrhythmogenesis.Biomedicines · 2026Review
- Selective RyR2 inhibition reduces arrhythmia susceptibility in human cardiac slices.The Journal of physiology · 2026Article
- Ryanodine receptor 2 mutations in catecholaminergic polymorphic ventricular tachycardia: From molecular mechanisms to precision medicine.World journal of cardiology · 2026Review
- Cyclic AMP-dependent regulation of ryanodine receptors in healthy and diseased hearts.Journal of molecular and cellular cardiology · 2026Review
- Multiscale stochastic modeling for calcium dynamics in cardiac electrophysiology: assessing whole-cell model reliability under phosphorylation and LCC downregulation.Frontiers in network physiology · 2026Article
- Cryo-EM Brings the Mechanisms of Activation, Inactivation, and Inhibition of Ryanodine Receptors into Focus.Advances in experimental medicine and biology · 2026Review
- Adenosine and acute low oxygen conditions suppress urinary bladder contractility through the activation of adenosine 2B receptors and large-conductance calcium-activated potassium channels.The Journal of physiology · 2026Article
- Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.The Journal of physiology · 2025Article
- A spatial single-cell atlas of the claustro-insular region uncovers key regulators of neuronal identity and excitability.Nature communications · 2025Article
- Review
- Preventing the phosphorylation of RyR2 at canonical sites reduces CaNature cardiovascular research · 2025Article
- Wnt/β-catenin pathway induces cardiac dysfunction via AKAP6-mediated RyR2 phosphorylation and sarcoplasmic reticulum calcium leakage.Journal of molecular cell biology · 2025Article
- Electrophysiological Mechanisms and Therapeutic Potential of Calcium Channels in Atrial Fibrillation.Reviews in cardiovascular medicine · 2025Review
- β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro.Pharmacology research & perspectives · 2025Article
- Dysregulated calcium signaling in the aged primate association cortices: vulnerability to Alzheimer's disease neuropathology.Frontiers in aging neuroscience · 2025Review
- Aging-associated mechanisms of atrial fibrillation progression and their therapeutic potential.The journal of cardiovascular aging · 2024Article
134 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defective regulation of the cardiac ryanodine receptor (RyR2)/calcium release channel, required for excitation-contraction coupling in the heart, has been linked to cardiac arrhythmias and heart failure. For example, diastolic calcium "leak" via RyR2 channels in the sarcoplasmic reticulum has been identified as an important factor contributing to impaired contractility in heart failure and ventricular arrhythmias that cause sudden cardiac death. In patients with heart failure, chronic activation of the "fight or flight" stress response leads to protein kinase A (PKA) hyperphosphorylation of RyR2 at Ser-2808. PKA phosphorylation of RyR2 Ser-2808 reduces the binding affinity of the channel-stabilizing subunit calstabin2, resulting in leaky RyR2 channels. We developed RyR2-S2808A mice to determine whether Ser-2808 is the functional PKA phosphorylation site on RyR2. Furthermore, mice in which the RyR2 channel cannot be PKA phosphorylated were relatively protected against the development of heart failure after myocardial infarction. Taken together, these data show that PKA phosphorylation of Ser-2808 on the RyR2 channel appears to be a critical mediator of progressive cardiac dysfunction after myocardial infarction.
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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.