Aim: 

Aquaporin-4 (AQP4) is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers. It is associated with the protein complex formed by dystrophin (DGC) and its expression is regulated by muscle activity. However, its physiological function in skeletal muscle is still unclear.

Methods: 

In this study, a detailed characterization of baseline fibre muscle features in 3 months-old AQP4 null mice has been performed, which includes cross-sectional area (CSA), fibre-type distribution, succinate dehydrogenase (SDH) activity, DGC protein expression and muscle water content.

Results: 

No differences in muscle water content and DGC expression between wild type and AQP4 null mice. CSA and SDH activity in extensor digitorum longus (EDL) and soleus, a fast- and slow-twitch muscle respectively, were then compared. Results obtained in EDL from AQP4 null mice showed a significant decrease in CSA of IIb-type fibres and a parallel increase in their oxidative activity (+19,9%, ±3,69), whereas no significant changes occurred in IIx- and IIa-type fibres and, generally, in fibre-type distribution. Interestingly, in the Soleus, that weakly express AQP4 in wild type, a significant reduction of IIa-type fibres (-10,94%, ±3,4) and an increase in their CSA were detected. Preliminary results on the mice voluntary activity showed much lower daily running distances of AQP4-KO mice compared to age and sex matched control animals in the first week of free wheel running exercise (ctrl: 6,82km, ±0,74, n=6; AQP4-KO: 2,72km, ±0,42, n=6).

Conclusion: 

Our findings suggest that AQP4-KO mice could be less fatigue resistant and the absence of AQP4 may compromise muscle function through the alteration in the mechanisms that regulate fibre volume during contraction.