ArticleThe Journal of general physiology2003
The pore region of the skeletal muscle ryanodine receptor is a primary locus for excitation-contraction uncoupling in central core disease.
Article in The Journal of general physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 79 citations in OpenAlex.
- Trial
- Article
- Cryo-EM Brings the Mechanisms of Activation, Inactivation, and Inhibition of Ryanodine Receptors into Focus.Advances in experimental medicine and biology · 2026Review
- RyR1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dual role of the S5 segment in type 1 ryanodine receptor channel gating.Communications biology · 2024Article
- RYR-1-Related Diseases International Research Workshop: From Mechanisms to Treatments Pittsburgh, PA, U.S.A., 21-22 July 2022.Journal of neuromuscular diseases · 2023Article
- Mutations in proteins involved in E-C coupling and SOCE and congenital myopathies.The Journal of general physiology · 2022Review
- Article
- Altered CaMetabolites · 2021Review
- Structural basis for diamide modulation of ryanodine receptor.Nature chemical biology · 2020Article
- Clinical Observation: Effect of a Second Transpositioned Variant in a Family with Autosomal Dominant Ryanodine Receptor-1-Related Disease.Journal of pediatric genetics · 2020Article
- Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990-2019.Orphanet journal of rare diseases · 2020Article
- The couplonopathies: A comparative approach to a class of diseases of skeletal and cardiac muscle.The Journal of general physiology · 2015Review
- Article
- Novel excitation-contraction uncoupled RYR1 mutations in patients with central core disease.Neuromuscular disorders : NMD · 2013Article
- Disease mutations in the ryanodine receptor N-terminal region couple to a mobile intersubunit interface.Nature communications · 2013Article
- Ca2+ release in muscle fibers expressing R4892W and G4896V type 1 ryanodine receptor disease mutants.PloS one · 2013Article
- Defects in Ca2+ release associated with local expression of pathological ryanodine receptors in mouse muscle fibres.The Journal of physiology · 2011Article
- Calcitonin gene-related peptide restores disrupted excitation-contraction coupling in myotubes expressing central core disease mutations in RyR1.The Journal of physiology · 2011Article
- Muscle weakness in Ryr1I4895T/WT knock-in mice as a result of reduced ryanodine receptor Ca2+ ion permeation and release from the sarcoplasmic reticulum.The Journal of general physiology · 2011Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Human central core disease (CCD) is caused by mutations/deletions in the gene that encodes the skeletal muscle ryanodine receptor (RyR1). Previous studies have shown that CCD mutations in the NH2-terminal region of RyR1 lead to the formation of leaky SR Ca2+ release channels when expressed in myotubes derived from RyR1-knockout (dyspedic) mice, whereas a COOH-terminal mutant (I4897T) results in channels that are not leaky to Ca2+ but lack depolarization-induced Ca2+ release (termed excitation-contraction [EC] uncoupling). We show here that store depletion resulting from NH2-terminal (Y523S) and COOH-terminal (Y4795C) leaky CCD mutant release channels is eliminated after incorporation of the I4897T mutation into the channel (Y523S/I4897T and Y4795C/I4897T). In spite of normal SR Ca2+ content, myotubes expressing the double mutants lacked voltage-gated Ca2+ release and thus exhibited an EC uncoupling phenotype similar to that of I4897T-expressing myotubes. We also show that dyspedic myotubes expressing each of seven recently identified CCD mutations located in exon 102 of the RyR1 gene (G4890R, R4892W, I4897T, G4898E, G4898R, A4905V, R4913G) behave as EC-uncoupled release channels. Interestingly, voltage-gated Ca2+ release was nearly abolished (reduced approximately 90%) while caffeine-induced Ca2+ release was only marginally reduced in R4892W-expressing myotubes, indicating that this mutation preferentially disrupts voltage-sensor activation of release. These data demonstrate that CCD mutations in exon 102 disrupt release channel permeation to Ca2+ during EC coupling and that this region represents a primary molecular locus for EC uncoupling in CCD.
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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.