AQP4-dependent water transport plays a functional role in exercise-induced skeletal muscle adaptations
Authors: Angelo Sparaneo
Antonio Frigeri
Maria Grazia Mola
Maria Svelto
Bert Blaauw
Carlo Reggiani
Francesco Pisani
Davide Basco
Grazia Paola Nicchia
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Aquaporin-4; skeletal muscle; physical activity; osmotic behavior; muscle contractile properties
Affiliations: Department of Bioscience, Biotechnologies and Biopharmaceutics and Center of Excellence in Comparative Genomics (CEGBA), University of Bari, Bari, Italy.

Abstract:  In this study we assess the functional role of Aquaporin-4 (AQP4) in the skeletal muscle by analyzing whether physical activity modulates AQP4 expression and whether the absence of AQP4 has an effect on osmotic behavior, muscle contractile properties, and physical activity. To this purpose, rats and mice were trained on the treadmill for 10 (D10) and 30 (D30) days and tested with exercise to exhaustion, and muscles were used for immunoblotting, RT-PCR, and fiber-type distribution analysis. Taking advantage of the AQP4 KO murine model, functional analysis of AQP4 was performed on dissected muscle fibers and sarcolemma vesicles. Moreover, WT and AQP4 KO mice were subjected to both voluntary and forced activity. Rat fast-twitch muscles showed a twofold increase in AQP4 protein in D10 and D30 rats compared to sedentary rats. Such increase positively correlated with the animal performance, since highest level of AQP4 protein was found in high runner rats. Interestingly, no shift in muscle fiber composition nor an increase in AQP4-positive fibers was found. Furthermore, no changes in AQP4 mRNA after exercise were detected, suggesting that post-translational events are likely to be responsible for AQP4 modulation. Experiments performed on AQP4 KO mice revealed a strong impairment in osmotic responses as well as in forced and voluntary activities compared to WT mice, even though force development amplitude and contractile properties were unvaried. Our findings definitively demonstrate the physiological role of AQP4 in supporting muscle contractile activity and metabolic changes that occur in fast-twitch skeletal muscle during prolonged exercise. 

Retracted: No

PubPeer comments:
 This article has a June 2013 correction at https: journals.plos.org plosone article?id=10.1371 annotation 86fc2632-913c-490d-8b9b-e925b38baec5 , which reads: *The legends for Figures 2 through 8 are incorrect. The figure under which the legend begins  Figure 3... is Figure 2, the figure under which the legend begins  Figure 4... is Figure 3, the figure under which the legend begins  Figure 5... is Figure 4, the figure under which the legend begins  Figure 6... is Figure 5, the figure under which the legend begins  Figure 7... is Figure 6, the figure under which the legend begins  Figure 8... is Figure 7, and the figure under which the legend does not begin with a numeric label is Figure 8.* , 
 Apart from the legend mishap, there are additional potential problems in Figures 1, 2, and 4. As shown in this illustration, several bands within the same panel appear to look similar to each other. Boxes of the same color focus attention to these similarities. Reported to the journal in 2015, but no action yet. ![file] ,