ArticleBiophysical journal2004
Distinct effects on Ca2+ handling caused by malignant hyperthermia and central core disease mutations in RyR1.
Article in Biophysical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
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- Complementary Roles of Structure and Variant Effect Predictors in RyR1 Clinical Interpretation.Human mutation · 2025Article
- Dual role of the S5 segment in type 1 ryanodine receptor channel gating.Communications biology · 2024Article
- A novel, patient-derived RyR1 mutation impairs muscle function and calcium homeostasis in mice.The Journal of general physiology · 2024Article
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- Mutations in proteins involved in E-C coupling and SOCE and congenital myopathies.The Journal of general physiology · 2022Review
- Molecular mechanism of the severe MH/CCD mutation Y522S in skeletal ryanodine receptor (RyR1) by cryo-EM.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Dominant or recessive mutations in theActa myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2020Article
- Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature.Skeletal muscle · 2020Review
- 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
- Insights into channel modulation mechanism of RYR1 mutants using Ca2+ imaging and molecular dynamics.The Journal of general physiology · 2020Article
- Cored in the act: the use of models to understand core myopathies.Disease models & mechanisms · 2019Review
- Severe Neonatal RYR1 Myopathy With Pathological Features of Congenital Muscular Dystrophy.Journal of neuropathology and experimental neurology · 2019Article
- Role of STIM1/ORAI1-mediated store-operated CaCell calcium · 2018Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Malignant hyperthermia (MH) and central core disease (CCD) are disorders of skeletal muscle Ca2+ homeostasis that are linked to mutations in the type 1 ryanodine receptor (RyR1). Certain RyR1 mutations result in an MH-selective phenotype (MH-only), whereas others result in a mixed phenotype (MH + CCD). We characterized effects on Ca2+ handling and excitation-contraction (EC) coupling of MH-only and MH + CCD mutations in RyR1 after expression in skeletal myotubes derived from RyR1-null (dyspedic) mice. Compared to wild-type RyR1-expressing myotubes, MH + CCD- and MH-only-expressing myotubes exhibited voltage-gated Ca2+ release (VGCR) that activated at more negative potentials and displayed a significantly higher incidence of spontaneous Ca2+ oscillations. However, maximal VGCR was reduced only for MH + CCD mutants (Y4795C, R2435L, and R2163H) in which spontaneous Ca2+ oscillations occurred with significantly longer duration (Y4795C and R2435L) or higher frequency (R2163H). Notably, myotubes expressing these MH + CCD mutations in RyR1 exhibited both increased [Ca2+]i and reduced sarcoplasmic reticulum (SR) Ca2+ content. We conclude that MH-only mutations modestly increase basal release-channel activity in a manner insufficient to alter net SR Ca2+ content ("compensated leak"), whereas the mixed MH + CCD phenotype arises from mutations that enhance basal activity to a level sufficient to promote SR Ca2+ depletion, elevate [Ca2+]i, and reduce maximal VGCR ("decompensated leak").
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Registered trials
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