Marked decrease of aquaporin-4 protein is independent of the changes in α1-syntrophin and TRPV4 levels in response to denervation-induced muscle atrophy in vivo.

Abstract

Aquaporin-4 (AQP4) is a selective water channel mediating water transport across cell membranes in skeletal muscles. Recently, it was noted that AQP4 is one of the key molecules regulating muscle morphology. Indeed, the AQP4 accumulation level was stably maintained in hypertrophied skeletal muscles. On the other hand, whether the AQP4 accumulation level is stably maintained in atrophied muscles remains poorly understood. The present study investigated the changes in the AQP4 accumulation level in the atrophied muscles at 2 weeks after denervation. As a result, the accumulation level of AQP4 in the atrophied muscle was significantly decreased compared with that in the control muscle (p < 0.05). Interestingly, the accumulation level of α1-syntrophin, which is an essential factor in regulating the stable accumulation level of AQP4, was stably maintained in the atrophied muscles. On the other hand, the accumulation level of the transient receptor potential vanilloid 4 (TRPV4), which contributes to cell volume control via interaction with AQP4, was significantly increased in the atrophied muscles compared with that in the control muscle (p < 0.05). Therefore, the present study suggested that the imbalance between the AQP4 accumulation level and skeletal muscle volume may be induced in the atrophied muscles by denervation, and the decrease in the accumulation level of AQP4 may be accompanied by defects in the functional and structural relationships with α1-syntrophin and TRPV4.