ArticleCirculation2010
Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure.
Article in Circulation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers.
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Who cites it
186 citing papers in PubMed, 303 citations in OpenAlex.
- Trial
- Dynamic-Structure Redesign of Calmodulin Reveals Mechanistic Constraints on Ryr2 Regulation.bioRxiv : the preprint server for biology · 2026Article
- Structural and Functional Regulation of RyR2 in Cardiac Calcium Handling and Arrhythmogenesis.Biomedicines · 2026Review
- Danhong Injection targets CaMKII through Dihydrotanshinone I to alleviate cardiomyocyte death and inflammation in viral myocarditis.Science China. Life sciences · 2026Article
- Cyclic AMP-dependent regulation of ryanodine receptors in healthy and diseased hearts.Journal of molecular and cellular cardiology · 2026Review
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 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
- Decreased RYR2 Cluster Size and Abnormal SR CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Activated CaMKIIδ translocates to the RyR nanodomain in cardiomyocytes.Cardiovascular research · 2025Article
- Targeting Calcium Regulation for Heart Failure and Arrhythmia Therapeutics: A Critical Review.Circulation · 2025Review
- Preventing the phosphorylation of RyR2 at canonical sites reduces CaNature cardiovascular research · 2025Article
- Macrophage-mediated IL-6 signaling drives ryanodine receptor-2 calcium leak in postoperative atrial fibrillation.The Journal of clinical investigation · 2025Article
- Heritability of sudden cardiac death in Thoroughbred racehorses.Equine veterinary journal · 2025Article
- Tetramethylpyrazine Protects Against Chronic Hypobaric Hypoxia-Induced Cardiac Dysfunction by Inhibiting CaMKII Activation in a Mouse Model Study.International journal of molecular sciences · 2024Article
- Article
- Left Ventricular Systolic Dysfunction in NBCe1-B/C-Knockout Mice.International journal of molecular sciences · 2024Article
- Ca2+/calmodulin-dependent kinase IIδC-induced chronic heart failure does not depend on sarcoplasmic reticulum Ca2+ leak.ESC heart failure · 2024Article
- Rare Variant inCirculation. Genomic and precision medicine · 2024Article
- Calpain inhibition takes center stage against atrial fibrillation in the diabetic heart.Heart rhythm · 2024Article
- Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control.Cardiovascular research · 2024Article
126 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundapproximately half of patients with heart failure die suddenly as a result of ventricular arrhythmias. Although abnormal Ca(2+) release from the sarcoplasmic reticulum through ryanodine receptors (RyR2) has been linked to arrhythmogenesis, the molecular mechanisms triggering release of arrhythmogenic Ca(2+) remain unknown. We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias. METHODS AND
resultsmice in which the S2814 Ca(2+)/calmodulin-dependent protein kinase II site on RyR2 is constitutively activated (S2814D) develop pathological sarcoplasmic reticulum Ca(2+) release events, resulting in reduced sarcoplasmic reticulum Ca(2+) load on confocal microscopy. These Ca(2+) release events are associated with increased RyR2 open probability in lipid bilayer preparations. At baseline, young S2814D mice have structurally and functionally normal hearts without arrhythmias; however, they develop sustained ventricular tachycardia and sudden cardiac death on catecholaminergic provocation by caffeine/epinephrine or programmed electric stimulation. Young S2814D mice have a significant predisposition to sudden arrhythmogenic death after transverse aortic constriction surgery. Finally, genetic ablation of the Ca(2+)/calmodulin-dependent protein kinase II site on RyR2 (S2814A) protects mutant mice from pacing-induced arrhythmias versus wild-type mice after transverse aortic constriction surgery.
conclusionsour results suggest that Ca(2+)/calmodulin-dependent protein kinase II phosphorylation of RyR2 Ca(2+) release channels at S2814 plays an important role in arrhythmogenesis and sudden cardiac death in mice with heart failure.
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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.