ArticleCardiovascular research2012
Enhanced binding of calmodulin to the ryanodine receptor corrects contractile dysfunction in failing hearts.
Article in Cardiovascular research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Calmodulation meta-analysis: predicting calmodulin binding via canonical motif clustering.The Journal of general physiology · 2014Pooled it
- Catecholaminergic polymorphic ventricular tachycardia-linked ryanodine receptor variants exhibit domain-specific calcium leak and calmodulin affinity properties.The Journal of physiology · 2026Article
- Structural and Functional Regulation of RyR2 in Cardiac Calcium Handling and Arrhythmogenesis.Biomedicines · 2026Review
- Article
- Enhancing calmodulin binding to ryanodine receptor is crucial to limit neuronal cell loss in Alzheimer disease.Scientific reports · 2021Article
- Enhancing calmodulin binding to cardiac ryanodine receptor completely inhibits pressure-overload induced hypertrophic signaling.Communications biology · 2020Article
- Dantrolene prevents hepatic steatosis by reducing cytoplasmic CaBiochemistry and biophysics reports · 2020Article
- Sarcoplasmic reticulum calcium mishandling: central tenet in heart failure?Biophysical reviews · 2020Review
- Article
- 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
- Gene Transfer of Engineered Calmodulin Alleviates Ventricular Arrhythmias in a Calsequestrin-Associated Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia.Journal of the American Heart Association · 2018Article
- Redox Dependent Modifications of Ryanodine Receptor: Basic Mechanisms and Implications in Heart Diseases.Frontiers in physiology · 2018Review
- CaMKII-dependent phosphorylation of RyR2 promotes targetable pathological RyR2 conformational shift.Journal of molecular and cellular cardiology · 2016Article
- Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes.PloS one · 2015Article
- Cardiac hypertrophy associated with impaired regulation of cardiac ryanodine receptor by calmodulin and S100A1.American journal of physiology. Heart and circulatory physiology · 2013Article
- Interference with ERK(Thr188) phosphorylation impairs pathological but not physiological cardiac hypertrophy.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- mTOR signaling in mice with dysfunctional cardiac ryanodine receptor ion channel.Journal of receptor, ligand and channel researchArticle
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsThe channel function of the cardiac ryanodine receptor (RyR2) is modulated by calmodulin (CaM). However, the involvement of CaM in aberrant Ca(2+) release in diseased hearts remains unclear. Here, we investigated the pathogenic role of defective CaM binding to the RyR2 in the channel dysfunction associated with heart failure. METHODS AND
resultsThe involvement of CaM in aberrant Ca(2+) release was assessed in normal and pacing-induced failing canine hearts. The apparent affinity of CaM for RyR2 was considerably lower in failing sarcoplasmic reticulum (SR) compared with normal SR. Thus, the amount of CaM bound to RyR2 was markedly decreased in failing myocytes. Expression of the CaM isoform Gly-Ser-His-CaM (GSH-CaM), which has much higher binding affinity than wild-type CaM for RyR1, restored normal CaM binding to RyR2 in both SR and myocytes of failing hearts. The Ca(2+) spark frequency (SpF) was markedly higher and the SR Ca(2+) content was lower in failing myocytes compared with normal myocytes. The incorporation of GSH-CaM into the failing myocytes corrected the aberrant SpF and SR Ca(2+) content to normal levels.
conclusionReduced CaM binding to RyR2 seems to play a critical role in the pathogenesis of aberrant Ca(2+) release in failing hearts. Correction of the reduced CaM binding to RyR2 stabilizes the RyR2 channel function and thereby restores normal Ca(2+) handling and contractile function to failing hearts.
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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.