Titre :
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Sarcoplasmic reticulum calcium leak under resting conditions in normal and dystrophic skeletal muscle
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Auteurs :
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Xèmes Journées Annuelles de la Société française de Myologie (SFM) (14-16 novembre 2012; Grenoble (France)) ;
Robin G ;
Berthier C ;
Allard B
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Type de document :
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Article
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Editeur :
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Société Française de Myologie SFM, 2012
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Pages :
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p. 39
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Langues:
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Anglais
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Résumé :
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Depolarization of skeletal muscle fiber elicits a conformational change of the dihydropyridine receptor (DHPR) in the tubular membrane that controls the opening of the ryanodine receptor (RyR), the sarcoplasmic reticulum (SR) Ca2+ release channel. At rest, it is assumed that RyRs are kept in a closed state imposed by the repressive action of DHPRs and generate a weak Ca2+ leak. However, a direct control of RyRs gating by DHPRs has never been demonstrated in resting muscle fiber. We monitored slow changes in SR Ca2+ content using the Ca2+ indicator Fluo5N loaded in the SR of voltage-clamped mouse muscle fibers. We first showed that external Ca2+ removal and the dihydropyridine compound nifedipine induced a SR Ca2+ efflux at -80 mV and prevented SR Ca2+ refilling following depolarization-evoked SR Ca2+ depletion. The rate of SR Ca2+ efflux was also shown to be controlled in a voltage-dependent manner within a membrane potential range more negative than -50 mV. These results indicate that SR Ca2+ efflux through RyRs is actively controlled by DHPRs in resting skeletal muscle. Finally we demonstrated that the resting SR Ca2+ leak is significantly elevated in muscle fibers from the mdx mouse, the murine model of Duchenne Muscular Dystrophy. This elevated SR Ca2+ leak may contribute to alteration of Ca2+ homeostasis in mdx muscle.
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Voir aussi :
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