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 resting cytosolic free calcium concentration ([Ca²⁺]i) would precede reductions in protein content and maximal isometric tetanic force (Po) in mouse soleus muscle after initiation of hindlimb suspension. Methods: Female ICR mice (n = 42) were hindlimb suspended for 1, 2, 3, 5, of 7 d; weight-matched mice were used as controls. Following the hindlimb suspension, the left soleus muscle was used to determine Po in vitro and the right soleus muscle was used to determine protein content and [Ca²⁺]i via confocal laser scanning 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 and myofibrillar protein contents were reduced 27-29% and 30-34%, respectively, 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 [Ca²⁺]i may play a role in initiating soleus muscle atrophy.