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 Ca2+ 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 Ca2+ uptake, estimated by the Ca2+ release following exposure to caffeine, was significantly slower in mdx mice, while the maximal Ca2+ quantity did not differ in either type of skeletal muscle at either stage of development. In 4-week-old mice spontaneous sarcoplasmic reticulum Ca2+ leakage was observed in EDL and soleus fibres and this was more pronounced in mdx mice. In addition, the maximal Ca2+- activated tension was smaller in mdx than in normal fibres, while the Ca2+ 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 Ca2+-ATPase to load Ca2+ and a leaky sarcoplasmic reticulum membrane may be involved in the altered intracellular Ca2+ homeostasis.