Decrease in AQP4 expression level in atrophied skeletal muscles with innervation

Functional interaction between the selective water channel AQP4 and several ion channels, such as TRPV4, NKCC1, and Na⁺ /K⁺ -ATPase, closely participate to regulate osmotic homeostasis. In the skeletal muscles, the decrease in APQ4 expression due to denervation was followed by the restoration of AQP4 expression during reinnervation. These findings raised the possibility that innervation status is an essential factor to regulate AQP4 expression in the skeletal muscles. This study investigated this hypothesis using disuse muscle atrophy model with innervation. Adult female Fischer 344 rats (8 weeks of age) were randomly assigned to either control (C) or cast immobilization (IM) groups (n = 6 per group). Two weeks after cast immobilization, the tibialis anterior muscles of each group were removed and the expression levels of some target proteins were quantified by western blot analysis. The expression level of AQP4 significantly decreased at 2 weeks post-immobilization (p < 0.05). Moreover, the expression levels of TRPV4, NKCC1, and Na⁺ /K⁺ -ATPase significantly decreased at 2 weeks post-immobilization (p < 0.05). This study suggested that innervation status is not always a key regulatory factor to maintain the expression of AQP4 in the skeletal muscles. Moreover, the transport of water and ions by AQP4 may be changed during immobilization-induced muscle atrophy.