ArticleBiophysical journal2007
Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites.
Article in Biophysical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 147 citations in OpenAlex.
- Cryo-EM Brings the Mechanisms of Activation, Inactivation, and Inhibition of Ryanodine Receptors into Focus.Advances in experimental medicine and biology · 2026Review
- Novel Ca2+ wave mechanisms in cardiac myocytes revealed by multiscale Ca2+ release model.The Journal of general physiology · 2025Article
- Calcium signaling in postsynaptic mitochondria: mechanisms, dynamics, and role in ATP production.Frontiers in molecular neuroscience · 2025Review
- Allicin ameliorates acute myocardial infarction in rats by modulating calcium homeostasis in cardiomyocytes through the induction of hydrogen sulfide production.Frontiers in pharmacology · 2025Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.Journal of applied physics · 2023Article
- The interplay of inflammation, exosomes and CaCardiovascular diabetology · 2023Review
- The role of subunit cooperativity on ryanodine receptor 2 calcium signaling.Biophysical journal · 2023Article
- The function and regulation of calsequestrin-2: implications in calcium-mediated arrhythmias.Biophysical reviews · 2022Review
- A Type 2 Ryanodine Receptor Variant in the Helical Domain 2 Associated with an Impairment of the Adrenergic Response.Journal of personalized medicine · 2021Article
- In silico simulations reveal that RYR distribution affects the dynamics of calcium release in cardiac myocytes.The Journal of general physiology · 2021Article
- Simulating cardiac CaPflugers Archiv : European journal of physiology · 2021Article
- Elucidation of Cellular Mechanisms That Regulate the Sustained Contraction and Relaxation of the Mammalian Iris.Investigative ophthalmology & visual science · 2020Article
- 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
- Recruiting RyRs to Open in a CaBiophysical journal · 2020Article
- Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse.Journal of cell science · 2019Article
- Size Matters: Ryanodine Receptor Cluster Size Heterogeneity Potentiates Calcium Waves.Biophysical journal · 2019Article
- Stochastic coupled map model of subcellular calcium cycling in cardiac cells.Chaos (Woodbury, N.Y.) · 2019Article
- Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model:Frontiers in physiology · 2019Article
- Ryanodine Receptor Open Times Are Determined in the Closed State.Biophysical journal · 2018Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The free [Ca2+] in endoplasmic/sarcoplasmic reticulum Ca2+ stores regulates excitability of Ca2+ release by stimulating the Ca2+ release channels. Just how the stored Ca2+ regulates activation of these channels is still disputed. One proposal attributes luminal Ca2+-activation to luminal facing regulatory sites, whereas another envisages Ca2+ permeation to cytoplasmic sites. This study develops a unified model for luminal Ca2+ activation for single cardiac ryanodine receptors (RyR2) and RyRs in coupled clusters in artificial lipid bilayers. It is shown that luminal regulation of RyR2 involves three modes of action associated with Ca2+ sensors in different parts of the molecule; a luminal activation site (L-site, 60 microM affinity), a cytoplasmic activation site (A-site, 0.9 microM affinity), and a novel cytoplasmic inactivation site (I2-site, 1.2 microM affinity). RyR activation by luminal Ca2+ is demonstrated to occur by a multistep process dubbed luminal-triggered Ca2+ feedthrough. Ca2+ binding to the L-site initiates brief openings (1 ms duration at 1-10 s(-1)) allowing luminal Ca2+ to access the A-site, producing up to 30-fold prolongation of openings. The model explains a broad data set, reconciles previous conflicting observations and provides a foundation for understanding the action of pharmacological agents, RyR-associated proteins, and RyR2 mutations on a range of Ca2+-mediated physiological and pathological processes.
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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.