Aquaporin-4 (AQP4) water channel is expressed in the fast-twitch skeletal muscle fibres. To elucidate the role of this water channel in skeletal muscle physiology, functional and structural analysis were performed on sedentary and exercised AQP4-null mice.

We subjected male 3 months-old AQP4-null mice and relative WT (CD1) to free wheel running activity, intense and exhaustive exercise, and grip test. Furthermore, gastrocnemius muscle contractile performances were evaluated by "in vivo" experiments, while EDL and soleus contractile properties were analysed on isolated muscles ("ex vivo").

We found that muscles cross-sectional area and weight were strongly reduced in sedentary AQP4 null mice, suggesting that muscular atrophy occurred. When evaluating twitch times in soleus muscles, a typical slow-twitch muscle, AQP4-null mice consistently showed a slight increase in time to peak and then in fatigue resistance, whereas no differences were found in EDL and gastrocnemius performances. However, daily voluntary activity results showed that WT mice ran twice than AQP4 null mice (P=0.003; n=17). In the exhaustive exercise, AQP4 null mice ran half than WT at day 1 (P=0.02; n=12), and reduced by about 8-fold their daily distance compared to WT mice after seven days of exercise (P=0.002, n=12). Moreover, grip test revealed a reduction in the maximal force in AQP4 null mice (200 ±11 mN vs 162 ±10,8 mN; P=0,03; n=6).

These findings provide evidences about the pivotal role of AQP4 in skeletal muscle physiology in mice.