Effect of AQP1 knock out on mouse exercise tolerance

Abstract

The water channel Aquaporin 1 (AQP1) is widely expressed throughout the body. Our lab demonstrated that AQP1 also can act as a CO2 channel when heterologously expressed in oocytes or when studied in the intact proximal tubule. We hypothesized that AQP1 plays a physiologically important role in O2 transport. Because AQP1 is present at high levels in erythrocytes and the pulmonary capillary endothelium, we compared voluntary wheel running over a 24‐h period in AQP1‐null vs wild‐type mice under conditions of hypoxia (ambient [O2] = 16%), normoxia (21%), and hyperoxia (40%). For wild‐type mice, the distances run were 16%: 9.2 ± 0.5 km (n = 28), 21%: 10.7 ± 0.5 km (n = 37), and 40%: 12.1 ± 0.6 km (n = 21). For AQP1‐null mice, the distances were 16%: 4.7 ± 0.5 km (n = 8), 21%: 6.2 ± 0.6 km (n = 13), and 40%: 6.9 ± 0.6 km (n = 12). We performed a linear‐regression analysis of distance run as a function of AQP1 status and [O2], treating [O2] categorically in reference to 21% O2. The AQP1 knockout reduced the distance run by 4.7 ± 0.5 km (p < 0.001), adjusting for [O2]. Compared to 21% O2, reducing [O2] to 16% reduced the distance run by 1.6 ± 0.6 km (p = 0.01), whereas increasing [O2] to 40% increased the distance run by 1.2 ± 0.6 km (p = 0.04), adjusting for AQP1 status. Thus, AQP1‐null mice have a major defect in voluntary exercise tolerance, consistent with the hypothesis that AQP1 plays an important physiological role in O2 transport across plasma membranes.