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To study the molecular basis of the prevention of muscle atrophy in hibernators,we investigated the regulation of cytosolic calcium and sarcoplasmic reticulum calcium of skeletal muscle fibers in hibernating Daurian ground squirrels and hindlimb-unloaded animals.Daurian ground squirrels (Spermophilus dauricus) were randomly assigned to a 7-group design (n=8/group) : Summer group (SUM) ,Autumn/before hibernation group (AUT/Pre-H) ,Autumn hindlimb-unloading group (AUT-HLU) ,hibernation group (H) ,interbout arousal group (IB-A) ,torpor again after interbout arousal group (H Next-) and a post-hibernation group (Post-H) .Rats were randomly assigned to a 2-group design (N=6/group) : synchronous control (CON) and hindlimb-unloaded (HLU) .Enzyme activity was determined by Fiske Subbarow.SERCA2 (sarcroplasmic reticulum Ca2+ transport ATPase) protein expression was determined by Western blotting.Our results show that: 1.Expression of SERCA2 was more sensitive to muscle disuse than Ca2+-ATPase and Na+,K+-ATPase activity of skeletal muscle fibers.2.The calcium regulation of slow soleus fibers was more sensitive to muscle disuse than that of fast extensor digitorum longus fibers.3.The calcium regulation during non-hibernation period was more sensitive to muscle disuse than during hibernation.4.Calcium regulation of rats was more sensitive to muscle disuse than Daurian ground squirrels.