title: [Molecular pathology of malignant hyperthermia and central core disease].
abstract: Recent advances of research on malignant hyperthermia(MH) were reviewed. The rate of Ca-induced Ca release(CICR) from the sarcoplasmic reticulum(SR) was measured on the skinned muscle fiber preparation of porcine and human MH. The rate of CICR was significantly increased both in porcine and human MH. These observations supported conclusion obtained by genetical studies that the ryanodine receptor (RYR1) was site of abnormality in most of porcine and part of human MH. The RYR1 is Ca release channel of skeletal muscle SR and CICR is one of main function of the channel. Subsequently, point mutation of RYR1 gene was found in the foot domain of the molecule. Heretofore, 9 kind of mutations were described in association of MH-susceptible(MHS) trait. 4 of them were accompanied by a form of congenital myopathy, central core disease(CCD). CCD is considered as an allelic disease of MH. But pathogenesis of peculiar morphological abnormality of CCD is mostly unknown. Mutations are identified only in half of familial MH cases, suggesting MH is heterogeneous. Recently, it was reported that mutation of the dihydropyridine receptor gene was associated with MHS in a french family. The dihydropyridine receptor is distributed on the transverse tubule membrane and constitutes the triad structure with RYR1.
authors.affiliation: Toranomon Hospital.
authors.forename: A
authors.initials: A
authors.lastname: Takagi
mesh_terms: D000483:Alleles; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type; D006579:Heterozygote; D006801:Humans; D008305:Malignant Hyperthermia / Q000235:genetics*; D017696:Myopathies, Nemaline / Q000235:genetics*; D017354:Point Mutation; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013552:Swine
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium