ArticleCardiovascular research2011
The relationship between arrhythmogenesis and impaired contractility in heart failure: role of altered ryanodine receptor function.
Article in Cardiovascular research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 120 citations in OpenAlex.
- Restoration of mitochondrial CaJournal of molecular and cellular cardiology · 2026Article
- The emerging role of calsequestrin 2: from calcium sensor and modulator to arrhythmia driver.Journal of physiology and biochemistry · 2026Review
- Targeting ryanodine receptors with allopurinol and xanthine derivatives for the treatment of cardiac and musculoskeletal weakness disorders.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Conditional ablation of MCU exacerbated cardiac pathology in a genetic arrhythmic model of CPVT.Journal of molecular and cellular cardiology plus · 2024Article
- Left Ventricular Systolic Dysfunction in NBCe1-B/C-Knockout Mice.International journal of molecular sciences · 2024Article
- A dual-targeted drug inhibits cardiac ryanodine receptor CaLife science alliance · 2024Article
- mROS‑calcium feedback loop promotes lethal ventricular arrhythmias and sudden cardiac death in early myocardial ischemia.International journal of molecular medicine · 2024Article
- New N-aryl-N-alkyl-thiophene-2-carboxamide compound enhances intracellular CaBiophysical journal · 2023Article
- The goldfish Carassius auratus: an emerging animal model for comparative cardiac research.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2022Review
- ER stress and calcium-dependent arrhythmias.Frontiers in physiology · 2022Review
- Ventricular Arrhythmias in Ischemic Cardiomyopathy-New Avenues for Mechanism-Guided Treatment.Cells · 2021Review
- Mechanisms underlying pathological CaPflugers Archiv : European journal of physiology · 2021Review
- RyR2 and Calcium Release in Heart Failure.Frontiers in physiology · 2021Review
- Melatonin to Rescue the Aged Heart: Antiarrhythmic and Antioxidant Benefits.Oxidative medicine and cellular longevity · 2021Review
- Understanding How Phosphorylation and Redox Modifications Regulate Cardiac Ryanodine Receptor Type 2 Activity to Produce an Arrhythmogenic Phenotype in Advanced Heart Failure.ACS pharmacology & translational science · 2020Review
- Tetrodotoxin-Sensitive Neuronal-Type NaJournal of the American Heart Association · 2020Article
- Increased RyR2 activity is exacerbated by calcium leak-induced mitochondrial ROS.Basic research in cardiology · 2020Article
- Conditional Up-Regulation of SERCA2a Exacerbates RyR2-Dependent Ventricular and Atrial Arrhythmias.International journal of molecular sciences · 2020Article
- Exercise Training Stabilizes RyR2-Dependent CaFrontiers in cardiovascular medicine · 2020Article
- Excitation-Contraction Coupling in the Goldfish (Frontiers in physiology · 2020Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aimsIn heart failure (HF), abnormal myocyte Ca(2+) handling has been implicated in cardiac arrhythmias and contractile dysfunction. In the present study, we investigated the relationships between Ca(2+) handling, reduced myocyte contractility, and enhanced arrhythmogenesis during HF progression in a canine model of non-ischaemic HF. METHODS AND
resultsKey Ca(2+) handling parameters were determined by measuring cytosolic and intra-sarcoplasmic reticulum (SR) [Ca(2+)] in isolated ventricular myocytes at different stages of HF. The progression of HF was associated with an early and continuous increase in ryanodine receptor (RyR2)-mediated SR Ca(2+) leak. The increase in RyR2 activity was paralleled by an increase in the frequency of diastolic spontaneous Ca(2+) waves (SCWs) in HF myocytes under conditions of β-adrenergic stimulation. In addition to causing arrhythmogenic-delayed afterdepolarizations, SCWs decreased the amplitude of subsequent electrically evoked Ca(2+) transients by depleting SR Ca(2+). At late stages of HF, Ca(2+) release oscillated essentially independent of electrical pacing. The increased propensity for the generation of SCWs in HF myocytes was attributable to reduced ability of the RyR2 channels to become refractory following Ca(2+) release. The progressive alterations in RyR2 function and Ca(2+) cycling in HF myocytes were associated with sequential modifications of RyR2 by CaMKII-dependent phosphorylation and thiol oxidation.
conclusionThese findings suggest that destabilized RyR2 activity due to excessive CaMKII phopshorylation and oxidation resulting in impaired post-release refractoriness is a common mechanism involved in arrhythmogenesis and contractile dysfunction in the failing heart.
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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.