ArticleNature medicine2014
The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed.
- Increased CaCells · 2026Article
- Structural and Functional Regulation of RyR2 in Cardiac Calcium Handling and Arrhythmogenesis.Biomedicines · 2026Review
- Ryanodine receptor 2 mutations in catecholaminergic polymorphic ventricular tachycardia: From molecular mechanisms to precision medicine.World journal of cardiology · 2026Review
- Calcium release channel deficiency syndrome in patients diagnosed with idiopathic ventricular fibrillation and decedents classified as sudden unexplained death in the young.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Cryo-EM Brings the Mechanisms of Activation, Inactivation, and Inhibition of Ryanodine Receptors into Focus.Advances in experimental medicine and biology · 2026Review
- Potentiation of ryanodine receptor-mediated calcium release by MAPK is responsible for epidermal transformation and carcinogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- Alda-1 attenuation of binge alcohol-caused atrial arrhythmias through a novel mechanism of suppressed c-Jun N-terminal Kinase-2 activity.Journal of molecular and cellular cardiology · 2024Article
- Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control.Cardiovascular research · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Long-Term Alcohol-Activated c-Jun N-terminal Kinase Isoform 2 Preserves Cardiac Function but Drives CaCells · 2023Article
- RCN2 promotes Nasopharyngeal carcinoma progression by curbing Calcium flow and Mitochondrial apoptosis.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Timing mechanisms to control heart rhythm and initiate arrhythmias: roles for intracellular organelles, signalling pathways and subsarcolemmal CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- "Dirty Dancing" of Calcium and Autophagy in Alzheimer's Disease.Life (Basel, Switzerland) · 2023Review
- Ligand sensitivity of type-1 inositol 1,4,5-trisphosphate receptor is enhanced by the D2594K mutation.Pflugers Archiv : European journal of physiology · 2023Article
- A Gating Mutation in Ryanodine Receptor Type 2 Rescues Phenotypes of Alzheimer's Disease Mouse Models by Upregulating Neuronal Autophagy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Increased β1-adrenergic receptor antibody confers a vulnerable substrate for atrial fibrillation via mediating Ca2+ mishandling and atrial fibrosis in active immunization rabbit models.Clinical science (London, England : 1979) · 2023Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors.
Funding
Abstract
Spontaneous Ca(2+) release from intracellular stores is important for various physiological and pathological processes. In cardiac muscle cells, spontaneous store overload-induced Ca(2+) release (SOICR) can result in Ca(2+) waves, a major cause of ventricular tachyarrhythmias (VTs) and sudden death. The molecular mechanism underlying SOICR has been a mystery for decades. Here we show that a point mutation, E4872A, in the helix bundle crossing region (the proposed gate) of the cardiac ryanodine receptor (RyR2) completely abolishes luminal, but not cytosolic, Ca(2+) activation of RyR2. The introduction of metal-binding histidines at this site converts RyR2 into a luminal Ni(2+)-gated channel. Mouse hearts harboring a heterozygous RyR2 mutation at this site (E4872Q) are resistant to SOICR and are completely protected against Ca(2+)-triggered VTs. These data show that the RyR2 gate directly senses luminal (store) Ca(2+), explaining the regulation of RyR2 by luminal Ca(2+), the initiation of Ca(2+) waves and Ca(2+)-triggered arrhythmias. This newly identified store-sensing gate structure is conserved in all RyR and inositol 1,4,5-trisphosphate receptor isoforms.
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