Evidence that AQP1 is a functional CO 2 channel in proximal tubules

AQP1 is a water channel that is extremely abundant in the proximal tubule (PT). Our previous work showed that basolateral CO 2 stimulates HCO 3 − reabsorption (J HCO3 ) by PT, and also that expressing AQP1 in Xenopus oocytes increases CO 2 permeability. To test the hypothesis that AQP1 functions as a CO 2 channel in the PT, we compared, in two kinds of studies, wild‐type (WT) and AQP1‐knockout (KO) mice with similar genetic backgrounds. In the first, we perfused the lumen of a mouse PT with 5% CO 2 /22 mM HCO 3 − /pH 7.4, and perfused the bath (B) with equilibrated or out‐of‐equilibrium (OOE) solutions with [HCO 3 − ] B = 22 mM, pH B = 7.4, and [CO 2 ] B = 0 – 20%. Compared to WT mice, AQP1 KO mice had a ~33% lower J HCO3 at 5% CO 2 (n = 9, P = 0.002) and a ~38% lower J HCO3 at 20% (n = 4, P = 0.013), but no difference at 0% (n = 5, P = 0.083). In the second study, we perfused the lumen with a CO 2 /HCO 3 − ‐free solution (pH 7.4), and perfused the bath with equilibrated or OOE CO 2 /HCO 3 − solutions (pH 7.4) to assess backflux (− J HCO3 ). At 0% CO 2 /22 mM HCO 3 − , J HCO3 was −37 ± 3 pmole mm −1 min −1 in WT mice (n = 4) and −33 ± 5 pmole mm −1 min −1 in AQP1 KO mice (n = 4; P = 0.53). At 5% CO 2 /22 mM HCO 3 − , J HCO3 was −74 ± 8 pmole mm − 1 min −1 in WT (n = 13) and −50 ± 5 pmole mm −1 min −1 in KO (n = 13; P = 0.012). At 20% CO 2 /0 mM HCO 3 − , J HCO3 was −39 ± 9 pmole mm −1 min −1 in WT (n = 4) and −13 ± 6 pmole mm −1 min −1 in KO (n = 5; P = 0.035). Our data indicate that AQP1 is important for HCO 3 − reabsorption, and that AQP1 is required for ~67% of the PT's CO 2 permeability.