Résumé :
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Sarcolemmopathies are muscular dystrophies caused by defects of proteins located within or near cell membrane. Underlying Pathological mechanisms remain unclear. Nevertheless, in dystrophin deficient mdx mice it has been shown that skeletal muscle fibers exhibited cytosolic Ca2+ overload due to an increased sarcolemmal permeability. Ultimately, Ca2+ dependant processes, such as proteolysis over-activation or mitochondrion dysfunction, have been proposed to trigger muscle fiber death. We challenged herein the calcium hypothesis in the delta-sarcoglycan deficient hamster CHF147 that developed muscular dystrophy mainly affecting proximal skeletal muscles. Using Fura-2, a fluorescent Ca2+ probe, we determined cytosolic Ca2+ level ([Ca2+]i) in mechanically dissected single skeletal muscle fibers (Quadriceps and EDL (extensor digitorum longus)) from control and CHF147 Syrian hamsters. Additionally, we evaluated sarcolemmal permeability to Ca2+ using the Mn2+ quenching method. In CHF147 skeletal muscle fibers the [Ca2+]i was significantly increased (p<0.05). This was more pronounced in Quadriceps fibers (In nM: 100.4 +/- 5.8 vs. 56.3 +/- 4.7 measured in control) than in EDL ones (in nM: 77.4 +/- 4.8 vs. 55.0 +/- 5.6 measured in control). In both muscle types from deficient delta-sarcoglycan hamsters, Mn2+ quench rate was two fold increased (in % of initial fluorescence vs. control value: Quadriceps: 10.2 +/- 1.3 vs.23.2 +/- 2.2; EDL: 8.9 +/- 0.7 vs.19.7 +/- 2.3; p<0.05). We verified that delta-sarcoglycan deficiency is associated with a cytosolic Ca2+ overload in striated muscles that appeared to depend on, at least in part, an increase in the sarcolemmal permeability to Ca2+. This may be a key determinant pathological step since [Ca2+]i was more elevated in CHF147 Quadriceps muscle fibers than in EDL ones, in respect to the more pronounced dystrophic phenotype observed in the former muscle. Further analysis are needed to precise the role of alterations in calcium homeostasis in the pathological process affecting delta-deficient muscle.
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