ArticleThe Journal of clinical investigation2010
Phosphorylation of the ryanodine receptor mediates the cardiac fight or flight response in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
111 citing papers in PubMed, 183 citations in OpenAlex.
- Trial
- Loss of phospholamban phosphorylation blunts CaJournal of molecular and cellular cardiology · 2026Article
- Effect of the gut microbiota metabolite phenylacetylglycine on cardiac CaBiophysical reports · 2026Article
- Structural and Functional Regulation of RyR2 in Cardiac Calcium Handling and Arrhythmogenesis.Biomedicines · 2026Review
- L-Type CaCirculation research · 2026Article
- Ryanodine receptor 2-mediated calcium leak is associated with increased glyoxalase I in the aging brain.JCI insight · 2025Article
- Targeting Calcium Regulation for Heart Failure and Arrhythmia Therapeutics: A Critical Review.Circulation · 2025Review
- 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
- Imaging Ca2+ Signals in Small Pulmonary Veins at Physiological Intraluminal Pressures.Journal of visualized experiments : JoVE · 2025Article
- Structural basis for ryanodine receptor type 2 leak in heart failure and arrhythmogenic disorders.Nature communications · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Personalized medicine in the dish to prevent calcium leak associated with short-coupled polymorphic ventricular tachycardia in patient-derived cardiomyocytes.Stem cell research & therapy · 2023Article
- Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.Biomolecules · 2023Review
- Heart failure-induced cognitive dysfunction is mediated by intracellular CaNature neuroscience · 2023Article
- RyR2 inhibition with dantrolene is antiarrhythmic, prevents further pathological remodeling, and improves cardiac function in chronic ischemic heart disease.Journal of molecular and cellular cardiology · 2023Article
- Molecular Aspects Implicated in Dantrolene Selectivity with Respect to Ryanodine Receptor Isoforms.International journal of molecular sciences · 2023Article
- Targeting ryanodine receptors to treat human diseases.The Journal of clinical investigation · 2023Review
- A Comprehensive Review of Dilated Cardiomyopathy in Pre-clinical Animal Models in Addition to Herbal Treatment Options and Multi-modality Imaging Strategies.Cardiovascular & hematological disorders drug targets · 2023Review
- Citrullination is linked to reduced CaActa physiologica (Oxford, England) · 2022Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
During the classic "fight-or-flight" stress response, sympathetic nervous system activation leads to catecholamine release, which increases heart rate and contractility, resulting in enhanced cardiac output. Catecholamines bind to β-adrenergic receptors, causing cAMP generation and activation of PKA, which phosphorylates multiple targets in cardiac muscle, including the cardiac ryanodine receptor/calcium release channel (RyR2) required for muscle contraction. PKA phosphorylation of RyR2 enhances channel activity by sensitizing the channel to cytosolic calcium (Ca²+). Here, we found that mice harboring RyR2 channels that cannot be PKA phosphorylated (referred to herein as RyR2-S2808A+/+ mice) exhibited blunted heart rate and cardiac contractile responses to catecholamines (isoproterenol). The isoproterenol-induced enhancement of ventricular myocyte Ca²+ transients and fractional shortening (contraction) and the spontaneous beating rate of sinoatrial nodal cells were all blunted in RyR2-S2808A+/+ mice. The blunted cardiac response to catecholamines in RyR2-S2808A+/+ mice resulted in impaired exercise capacity. RyR2-S2808A+/+ mice were protected against chronic catecholaminergic-induced cardiac dysfunction. These studies identify what we believe to be new roles for PKA phosphorylation of RyR2 in both the heart rate and contractile responses to acute catecholaminergic stimulation.
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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.