Time course changes in [Ca2+](i), force, and protein content in hindlimb-suspended mouse soleus muscles

Background: Exposure to reduced gravitational forces during spaceflight is associated with significant reductions in skeletal muscle mass and strength . The purpose of this study was to test the hypothesis that increases in re sting cytosolic free calcium concentration ([Ca2+](i)) would precede reduct ions in protein content and maximal isometric tetanic force (Po) in mouse s oleus muscle after initiation of hindlimb suspension. Methods: Female ICR m ice (n = 42) were hindlimb suspended for 1, 2, 3, 5, or 7 d; weight-matched mice were used as controls. Following the hindlimb suspension, the left so leus muscle was used to determine Po in vitro and the right soleus muscle w as used to determine protein content and [Ca2+](i) via confocal laser scann ing microscopy. Results: Compared with controls, [Ca2+](i) was elevated by 38% at 2 d, and 117% at 7 d. Compared with controls, soleus muscle total an d myofibrillar protein contents were reduced 27-29% and 30-34%, respectivel y, at 5-7 d after initiation of hindlimb suspension. Compared with controls , soleus muscle Po was decreased by 24% at 3 d, and 38% at 7 d. Conclusion: It appears that resting cytosolic Ca2+ homeostasis is disturbed soon after the initiation of hindlimb suspension, and these elevations in ICa2+]i may play a role in initiating soleus muscle atrophy.