Résumé :
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Communication n° 260. The muscular fatigue observed during prolonged activity of skeletal muscles induces a loss of functional capacity mainly due to a variety of metabolic changes, like acidosis, accumulation of inorganic phosphate (Pi), depletion in creatine phosphate (CP) and large production of reactive oxygen species. Muscles of patients with Duchenne muscular dystrophy (DMD), where the intracellular Ca2+ homeostasis is perturbed, are more susceptible to the deleterious effects of muscle exercise. These functional alterations in dystrophic muscle characteristics during fatigue could be explained in part by modifications of contractile proteins and sarcoplasmic reticulum (SR) properties. The aim of the present work is to study the effects of metabolic changes associated with fatigue (pH6.5, 0 CP, 15mM Pi) on contractile proteins and Ca2+ handling mechanisms in dystrophic skeletal muscle. This analysis was investigated in diaphragm muscle from mdx mice (C57Bl/10mdx, 16 weeks), an animal model for DMD, using physiological and biochemical techniques. When triton-skinned fibres were exposed to fatigue conditions, a drastic reduction in maximal Ca2+-activated tension and a decrease in Ca2+ sensitivity (Control: pCa50=5.91Æ0.02, Fatigue: pCa50=5.60Æ0.02, n=13) was observed. In diaphragm saponin-skinned fibres, where the SR was maintained functional, the Ca2+ uptake in presence of fatigue solution induced a decrease in 10 mM caffeine contracture amplitude. In addition, metabolic changes induced in SR vesicle preparations a decrease in maximal Ca2+ loading capacity, associated with a slow-down of the SR Ca2+-uptake rate. All these findings show that the rate of Ca2+ reuptake by the SR was strongly disturbed during fatigue process and could explain the loss of functional capacities in muscular dystrophies. Then proteins involved in the Ca2+ homeostasis would be potential targets to improve the fatigue resistance in muscle disorders.
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