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Contractile impairment and structural alterations of skeletal muscles from knockout mice lacking type 1 and type 3 ryanodine receptors
Author(s) -
Barone Virginia,
Bertocchini Federica,
Bottinelli Roberto,
Protasi Feliciano,
Allen Paul D.,
Franzini Armstrong Clara,
Reggiani Carlo,
Sorrentino Vincenzo
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00003-9
Subject(s) - ryanodine receptor , ryr1 , skeletal muscle , myofibril , endoplasmic reticulum , receptor , biology , gene isoform , microbiology and biotechnology , wild type , medicine , myocyte , muscle contraction , contraction (grammar) , chemistry , endocrinology , biochemistry , mutant , gene
Skeletal muscle contraction is triggered by the release of Ca 2+ from the sarcoplasmic reticulum through the type 1 ryanodine receptor (RyR1). Recently it has been shown that also the type 3 isoform of ryanodine receptor (RyR3), which is expressed in some mammalian skeletal muscles, may participate in the regulation of skeletal muscle contraction. Here we report the generation and the characterization of double mutant mice carrying a targeted disruption of both the RyR1 and the RyR3 genes (RyR1 −/− ;RyR3 −/− ). Skeletal muscles from mice homozygous for both mutations are unable to contract in response to caffeine and to ryanodine. In addition, they show a very poor capability to develop tension when directly activated with micromolar [Ca 2+ ] i after membrane permeabilization which indicates either poor development or degeneration of the myofibrils. This was confirmed by biochemical analysis of contractile proteins. Electron microscopy confirms small size of myofibrils and shows complete absence of feet (RyRs) in the junctional SR.