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Functional and Morphological Features of Skeletal Muscle from Mutant Mice Lacking Both Type 1 and Type 3 Ryanodine Receptors
Author(s) -
Ikemoto Takaaki,
Komazaki Shinji,
Takeshima Hiroshi,
Nishi Miyuki,
Noda Tetsuo,
Iino Masamitsu,
Endo Makoto
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.305bn.x
Subject(s) - ryanodine receptor , ryr1 , endoplasmic reticulum , skeletal muscle , myocyte , chemistry , triad (sociology) , ryanodine receptor 2 , medicine , calcium , intracellular , mitochondrion , mutant , microbiology and biotechnology , wild type , endocrinology , cardiac muscle , biology , biochemistry , gene , psychology , psychoanalysis
1 We generated mice with targeted disruptions in the genes for both ryanodine receptor type 1 (RyR‐1) and type 3 (RyR‐3) to study the functional roles of RyR subtypes in skeletal muscle. 2 In permeabilized myocytes lacking both the RyRs, the Ca 2+ ‐induced Ca 2+ release (CICR) mechanism was completely lost, and caffeine failed to induce Ca 2+ release. 3 Replacement of potassium methanesulphonate in an experimental intracellular solution with choline chloride resulted in Ca 2+ release in the wild‐type muscle but not in the mutant muscle lacking RyR‐1. 4 The double‐mutant mice exhibited more severe muscular degeneration than RyR‐1‐deficient mice with formation of large vacuoles and swollen mitochondria while structural coupling between T‐tubules and the sarcoplasmic reticulum was retained. 5 These results demonstrate that CICR is mediated solely by RyR‐1 and RyR‐3 in skeletal muscle cells, and suggest that RyR‐1 is involved in Cl − ‐induced Ca 2+ release. The results also suggest the presence of molecular components other than RyRs responsible for the triad formation. RyR‐3 may have a role in the normal morphogenesis of skeletal muscle cells, although functionally it can be replaced by RyR‐1.