ArticleThe Journal of cell biology2003
PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure.
Article in The Journal of cell biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 241 citations in OpenAlex.
- Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.Proceedings of the National Academy of Sciences of the United States of America · 2015Trial
- Aerobic exercise partially improves the skeletal muscle phenotype in a model of heart failure with preserved ejection fraction in male mice.Physiological reports · 2026Article
- Dysferlin and the Regulation of CaCells · 2025Review
- Phosphorylation of RYR1 at SerScience signaling · 2025Article
- Muscle-specific Ryanodine receptor 1 properties underlie limb-girdle muscular dystrophy 2B/R2 progression.Nature communications · 2025Article
- Universal Prime Editing Therapeutic Strategy for RyR1-Related Myopathies: A Protective Mutation Rescues Leaky RyR1 Channel.International journal of molecular sciences · 2025Article
- Genetic variation in RYR1 is associated with heart failure progression and mortality in a diverse patient population.Frontiers in cardiovascular medicine · 2025Article
- Stable oxidative posttranslational modifications alter the gating properties of RyR1.The Journal of general physiology · 2024Article
- Dual Roles of microRNA-122 in Hepatocellular Carcinoma and Breast Cancer Progression and Metastasis: A Comprehensive Review.Current issues in molecular biology · 2024Review
- Purinergic agonists increase [CaAmerican journal of physiology. Cell physiology · 2024Article
- Get Ready to Sharpen Your Tools: A Short Guide to Heterotrimeric G Protein Activity Biosensors.Molecular pharmacology · 2024Review
- RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-α/NF-κB/NLRP3 Signaling Pathway through Inhibiting Calcineurin.Journal of cardiovascular translational research · 2024Article
- Signalling of Adrenoceptors: Canonical Pathways and New Paradigms.Handbook of experimental pharmacology · 2024Review
- Ryanodine receptor inhibition with acute dantrolene treatment reduces arrhythmia susceptibility in human hearts.American journal of physiology. Heart and circulatory physiology · 2023Article
- Function of a mutant ryanodine receptor (T4709M) linked to congenital myopathy.Scientific reports · 2023Article
- Skeletal muscle atrophy, regeneration, and dysfunction in heart failure: Impact of exercise training.Journal of sport and health science · 2023Review
- Heart failure-induced cognitive dysfunction is mediated by intracellular CaNature neuroscience · 2023Article
- Defective cerebellar ryanodine receptor type 1 and endoplasmic reticulum calcium 'leak' in tremor pathophysiology.Acta neuropathologica · 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
53 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
17 authors at 3 institutions in 2 countries.
Funding
Abstract
The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is the major calcium (Ca2+) release channel required for skeletal muscle excitation-contraction (EC) coupling. RyR1 function is modulated by proteins that bind to its large cytoplasmic scaffold domain, including the FK506 binding protein (FKBP12) and PKA. PKA is activated during sympathetic nervous system (SNS) stimulation. We show that PKA phosphorylation of RyR1 at Ser2843 activates the channel by releasing FKBP12. When FKB12 is bound to RyR1, it inhibits the channel by stabilizing its closed state. RyR1 in skeletal muscle from animals with heart failure (HF), a chronic hyperadrenergic state, were PKA hyperphosphorylated, depleted of FKBP12, and exhibited increased activity, suggesting that the channels are "leaky." RyR1 PKA hyperphosphorylation correlated with impaired SR Ca2+ release and early fatigue in HF skeletal muscle. These findings identify a novel mechanism that regulates RyR1 function via PKA phosphorylation in response to SNS stimulation. PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF.
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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.