ArticleThe Biochemical journal2004
Central core disease mutations R4892W, I4897T and G4898E in the ryanodine receptor isoform 1 reduce the Ca2+ sensitivity and amplitude of Ca2+-dependent Ca2+ release.
Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Diagnostics and therapy of muscle channelopathies--Guidelines of the Ulm Muscle Centre.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2008Guideline
- Article
- Structural basis for diamide modulation of ryanodine receptor.Nature chemical biology · 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
- Pore dynamics and conductance of RyR1 transmembrane domain.Biophysical journal · 2014Article
- Novel excitation-contraction uncoupled RYR1 mutations in patients with central core disease.Neuromuscular disorders : NMD · 2013Article
- Ca2+ release in muscle fibers expressing R4892W and G4896V type 1 ryanodine receptor disease mutants.PloS one · 2013Article
- Calcitonin gene-related peptide restores disrupted excitation-contraction coupling in myotubes expressing central core disease mutations in RyR1.The Journal of physiology · 2011Article
- Single channel properties of heterotetrameric mutant RyR1 ion channels linked to core myopathies.The Journal of biological chemistry · 2008Article
- Ryanodine receptor type 1 (RyR1) possessing malignant hyperthermia mutation R615C exhibits heightened sensitivity to dysregulation by non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95).Neurotoxicology · 2007Article
- Central core disease.Orphanet journal of rare diseases · 2007Review
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Authors and funding
4 authors.
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Abstract
Three CCD (central core disease) mutants, R4892W (Arg4892-->), I4897T and G4898E, in the pore region of the skeletal-muscle Ca2+-release channel RyR1 (ryanodine receptor 1) were characterized using a newly developed assay that monitored Ca2+ release in the presence of Ca2+ uptake in microsomes isolated from HEK-293 cells (human embryonic kidney 293 cells), co-expressing each of the three mutants together with SERCA1a (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase 1a). Both Ca2+ sensitivity and peak amplitude of Ca2+ release were either absent from or sharply decreased in homotetrameric mutants. Co-expression of wild-type RyR1 with mutant RyR1 (heterotetrameric mutants) restored Ca2+ sensitivity partially, in the ratio 1:2, or fully, in the ratio 1:1. Peak amplitude was restored only partially in the ratio 1:2 or 1:1. Reduced amplitude was not correlated with maximum Ca2+ loading or the amount of expressed RyR1 protein. High-affinity [3H]ryanodine binding and caffeine-induced Ca2+ release were also absent from the three homotetrameric mutants. These results indicate that decreased Ca2+ sensitivity is one of the serious defects in these three excitation-contraction uncoupling CCD mutations. In CCD skeletal muscles, where a mixture of wild-type and mutant RyR1 is expressed, these defects are expected to decrease Ca2+-induced Ca2+ release, as well as orthograde Ca2+ release, in response to transverse tubular membrane depolarization.
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