Role of aquaporin 1 (AQP1) as a CO 2 channel in chronic metabolic acidosis

AQP1 expresses abundantly at proximal‐tubule (PT) apical and basolateral membranes, contributing to H 2 O and CO 2 permeability. Previous work showed that the knockout of AQP1 causes a ~50% fall in PT HCO 3 reabsorption, presumably by reducing apical CO 2 uptake. To test whether AQP1‐null mice (KO) have a decreased ability to resist acid loads, we catheterized the carotid artery of wild‐type (WT) and KO mice with a gas‐impermeable catheter, and imposed chronic metabolic acidosis (MAc) by adding 1% (WT) or 0.6% (KO) NH 4 Cl to the drinking water. The net NH 4 Cl loads were 2.67 (WT) vs 2.74 (KO) mg/day/gram body weight (p = 0.27). We collected arterial blood‐gas samples from conscious mice on days 0, 2 and 7. On day 0 (before challenge), pH, pCO 2 , and [HCO 3 ] were not different for WT vs KO. At day 2, arterial pH fell from 7.42 ± 0.01 (day‐0 value) to 7.37 ± 0.03 for WT, but from 7.45 ± 0.01 to 7.25 ± 0.02 for KO. Similarly, [HCO 3 ] fell from 21.4 ± 0.7 to 17.7 ± 0.9 mM (p < 0.01) for WT, but from 22.5 ± 0.6 to 13.9 ± 0.7 mM (p < 0.01) for KO. At day 7, the parameters recovered to day‐0 levels for WT, but for KO remained depressed: pH = 7.29 ± 0.02 (p < 0.01 vs day 0) and [HCO 3 ] = 16.2 ± 0.9 mM (p < 0.01 vs day 0). Values of pCO 2 (30 to 33 mm Hg) or body weight did not change significantly during the study for WT or KO. Thus, AQP1, presumably by acting as a CO 2 channel in the PT, plays an important physiological role in allowing the animal to stabilize arterial pH during chronic MAc.