ArticleThe Journal of membrane biology1995
Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle.
Article in The Journal of membrane biology, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 171 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
- Review
- Structure-based mechanism of RyR channel operation by calcium and magnesium ions.PLoS computational biology · 2025Article
- Article
- The biophysical properties of TRIC-A and TRIC-B and their interactions with RyR2.The Journal of general physiology · 2023Article
- EuBiophysical journal · 2023Article
- Dantrolene inhibition of ryanodine channels (RyR2) in artificial lipid bilayers depends on FKBP12.6.The Journal of general physiology · 2023Article
- FKBP12 binds to the cardiac ryanodine receptor with negative cooperativity: implications for heart muscle physiology in health and disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- A bivalent remipede toxin promotes calcium release via ryanodine receptor activation.Nature communications · 2023Article
- Structures of PKA-phospholamban complexes reveal a mechanism of familial dilated cardiomyopathy.eLife · 2022Article
- CaeLife · 2022Article
- Ryanodine receptor and immune-related molecules in diabetic cardiomyopathy.ESC heart failure · 2021Review
- Regulatory mechanisms of ryanodine receptor/CaJournal of muscle research and cell motility · 2021Review
- RYR2 Channel Inhibition Is the Principal Mechanism of Flecainide Action in CPVT.Circulation research · 2021Article
- The central domain of cardiac ryanodine receptor governs channel activation, regulation, and stability.The Journal of biological chemistry · 2020Article
- Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse.Journal of cell science · 2019Article
- Regulation of the RyR channel gating by CaBiophysical reviews · 2018Review
- Dysregulated ZnThe Journal of biological chemistry · 2017Article
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ca(2+)-dependent inhibition of native and isolated ryanodine receptor (RyR) calcium release channels from sheep heart and rabbit skeletal muscle was investigated using the lipid bilayer technique. We found that cytoplasmic Ca2+ inhibited cardiac RyRs with an average Km = 15 mM, skeletal RyRs with Km = 0.7 mM and with Hill coefficients of 2 in both isoforms. This is consistent with measurements of Ca2+ release from the sarcoplasmic reticulum (SR) in skinned fibers and with [3H]-ryanodine binding to SR vesicles, but is contrary to previous bilayer studies which were unable to demonstrate Ca(2+)-inhibition in cardiac RyRs (Chu, Fill, Stefani & Entman (1993) J. Membrane Biol. 135, 49-59). Ryanodine prevented Ca2+ from inhibiting either cardiac or skeletal RyRs. Ca(2+)-inhibition in cardiac RyRs appeared to be the most fragile characteristic of channel function, being irreversibly disrupted by 500 mM Cs+, but not by 500 mM K+, in the cis bath or by solublization with the detergent CHAPS. These treatments had no effect on channel regulation by AMP-PNP, caffeine, ryanodine, ruthenium red, or Ca(2+)-activation. Ca(2+)-inhibition in skeletal RyRs was retained in the presence of 500 mM Cs+. Our results provide an explanation for previous findings in which cardiac RyRs in bilayers with 250 mM Cs+ in the solutions fail to demonstrate Ca(2+)-inhibition, while Ca(2+)-inhibition of Ca2+ release is observed in vesicle studies where K+ is the major cation. A comparison of open and closed probability distributions from individual RyRs suggested that the same gating mechanism mediates Ca(2+)-inhibition in skeletal RyRs and cardiac RyRs, with different Ca2+ affinities for inhibition. We conclude that differences in the Ca(2+)-inhibition in cardiac and skeletal channels depends on their Ca2+ binding properties.
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