ArticleCardiovascular research2010
Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca(2+) release in heart failure.
Article in Cardiovascular research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 79 citations in OpenAlex.
- Trial
- Dynamic-Structure Redesign of Calmodulin Reveals Mechanistic Constraints on Ryr2 Regulation.bioRxiv : the preprint server for biology · 2026Article
- Growth-Associated Protein-43 Loss Promotes CaAntioxidants (Basel, Switzerland) · 2025Article
- Molecular Mechanism of a FRET Biosensor for the Cardiac Ryanodine Receptor Pathologically Leaky State.International journal of molecular sciences · 2023Article
- Dantrolene inhibition of ryanodine channels (RyR2) in artificial lipid bilayers depends on FKBP12.6.The Journal of general physiology · 2023Article
- Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR).Nature communications · 2023Article
- Molecular Mechanism of a FRET Biosensor for the Cardiac Ryanodine Receptor Pathologically Leaky State.bioRxiv : the preprint server for biology · 2023Article
- Dantrolene improves left ventricular diastolic property in mineralcorticoid-salt-induced hypertensive rats.Biochemistry and biophysics reports · 2023Article
- Characterization of N-terminal RYR2 variants outside CPVT1 hotspot regions using patient iPSCs reveal pathogenesis and therapeutic potential.Stem cell reports · 2022Article
- Therapeutic Approaches of Ryanodine Receptor-Associated Heart Diseases.International journal of molecular sciences · 2022Review
- CALM1 rs3179089 polymorphism might contribute to coronary artery disease susceptibility in Chinese male: a case-control study.Genes & genomics · 2022Article
- RyR2 and Calcium Release in Heart Failure.Frontiers in physiology · 2021Review
- Enhancing calmodulin binding to cardiac ryanodine receptor completely inhibits pressure-overload induced hypertrophic signaling.Communications biology · 2020Article
- The functional significance of redox-mediated intersubunit cross-linking in regulation of human type 2 ryanodine receptor.Redox biology · 2020Article
- Sarcoplasmic reticulum calcium mishandling: central tenet in heart failure?Biophysical reviews · 2020Review
- Pathophysiology of Calcium Mediated Ventricular Arrhythmias and Novel Therapeutic Options with Focus on Gene Therapy.International journal of molecular sciences · 2019Review
- Ryanodine receptor-bound calmodulin is essential to protect against catecholaminergic polymorphic ventricular tachycardia.JCI insight · 2019Article
- Calmodulin inhibition of human RyR2 channels requires phosphorylation of RyR2-S2808 or RyR2-S2814.Journal of molecular and cellular cardiology · 2019Article
- Nuclear translocation of calmodulin in pathological cardiac hypertrophy originates from ryanodine receptor bound calmodulin.Journal of molecular and cellular cardiology · 2018Article
- Estradiol Treatment Initiated Early After Ovariectomy Regulates Myocardial Gene Expression and Inhibits Diastolic Dysfunction in Female Cynomolgus Monkeys: Potential Roles for Calcium Homeostasis and Extracellular Matrix Remodeling.Journal of the American Heart Association · 2018Article
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsCalmodulin (CaM) is well known to modulate the channel function of the cardiac ryanodine receptor (RyR2). However, the possible role of CaM on the aberrant Ca(2+) release in diseased hearts remains unclear. In this study, we investigated the state of RyR2-bound CaM and channel dysfunctions in pacing-induced failing hearts. METHODS AND
resultsThe characteristics of CaM binding to RyR2 and the role of CaM on the aberrant Ca(2+) release were assessed in normal and failing canine hearts. The affinity of CaM binding to RyR2 was lower in failing sarcoplasmic reticulum (SR) than in normal SR. Addition of FK506, which dissociates FKBP12.6 from RyR2, to normal SR reduced the CaM-binding affinity. Dantrolene restored a normal level of the CaM-binding affinity in either FK506-treated (normal) SR or failing SR, suggesting that the defective inter-domain interaction between the N-terminal domain and the central domain of RyR2 (the therapeutic target of dantrolene) is involved in the reduction of the CaM-binding affinity in failing hearts. In saponin-permeabilized cardiomyocytes, the frequency of spontaneous Ca(2+) sparks was much more increased in failing cardiomyocytes than in normal cardiomyocytes, whereas the addition of a high concentration of CaM attenuated the aberrant increase of Ca(2+) sparks.
conclusionThe defective inter-domain interaction between N-terminal and central domains within RyR2 reduces the binding affinity of CaM to RyR2, thereby causing the spontaneous Ca(2+) release events in failing hearts. Correction of the defective CaM binding may be a new strategy to protect against the aberrant Ca(2+) release in heart failure.
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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.