Sarcoplasmic reticulum function in slow- and fast-twitch skeletal muscles from mdx mice.
The aim of the present study was to establish whether alterations in sarcoplasmic reticulum function are involved in the abnormal Ca(2+) homeostasis of skeletal muscle in mice with muscular dystrophy ( mdx). The properties of the sarcoplasmic reticulum and contractile proteins of fast- and slow-twitch muscles were therefore investigated in chemically skinned fibres isolated from the extensor digitorum longus (EDL) and soleus muscles of normal (C57BL/10) and mdx mice at 4 and 11 weeks of development. Sarcoplasmic reticulum Ca(2+) uptake, estimated by the Ca(2+) release following exposure to caffeine, was significantly slower in mdx mice, while the maximal Ca(2+) quantity did not differ in either type of skeletal muscle at either stage of development. In 4-week-old mice spontaneous sarcoplasmic reticulum Ca(2+) leakage was observed in EDL and soleus fibres and this was more pronounced in mdx mice. In addition, the maximal Ca(2+)-activated tension was smaller in mdx than in normal fibres, while the Ca(2+) sensitivity of the contractile apparatus was not significantly different. These results indicate that mdx hindlimb muscles are affected differently by the disease process and suggest that a reduced ability of the Ca(2+)-ATPase to load Ca(2+) and a leaky sarcoplasmic reticulum membrane may be involved in the altered intracellular Ca(2+) homeostasis.
Laboratoire de Physiologie Générale, UMR CNRS 6018, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, 44322 Nantes, Cedex 03, France.
Alexandra
A
Divet
Corinne
C
Huchet-Cadiou
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D016474:Weight-Bearing
D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D002118:Calcium