Regulation of glomerulotubular balance. IV. Implication of aquaporin 1 in flow-dependent proximal tubule transport and cell volume.

The water channel aquaporin-1 (AQP1) is the principal water pathway for isotonic water reabsorption in the kidney proximal tubule (PT). We investigated flow-mediated fluid ( J _v ) and [Formula: see text] ([Formula: see text]) reabsorption in PTs of the mouse kidney by microperfusion in wild-type (WT) and AQP1 knockout (KO) mice. Experiments were simulated in an adaptation of a mathematical model of the rat PT. An increase in perfusion rate from 5 to 20 nL/min increased J _v and [Formula: see text] in PTs of WT mice. AQP1 KO mice significantly decreased J _v at low and high flow rates compared with control. In contrast, [Formula: see text] was not reduced at either low or high flow rates. Cell volume showed no significant difference between WT and AQP1 KO mice. Renal clearance experiments showed significantly higher urine flow in AQP1 KO mice, but there was no significant difference in either Na ⁺ and K ⁺ or [Formula: see text] excretion. Acid-base parameters of blood pH, Pco ₂ , [Formula: see text], and urine pH were the same in both WT and KO mice. In model calculations, tubules whose tight junction (TJ) water permeability ( P _f ) was that assigned to the rat TJ, showed no difference in J _v between WT and KO, whereas TJ P _f set to 25% of the rat predicted J _v concordant with our observations from AQP1 KO. These results affirm the dominance of AQP1 in mediating isotonic water reabsorption by the mouse PT and demonstrate that flow-stimulated [Formula: see text] reabsorption is intact and independent of AQP1. With reference to the model, the findings also suggest that TJ water flux in the PT is less prominent in the mouse than in the rat kidney. NEW & NOTEWORTHY We found an absence of flow-dependent modulation of fluid absorption but no effect on either proximal tubule (PT) [Formula: see text] absorption or acid-base parameters in the aquaporin 1 (AQP1) knockout mouse. We affirmed the dominance of the water channel AQP1 in mediating isotonic water reabsorption by the mouse PT and demonstrated that flow-stimulated [Formula: see text] reabsorption is independent of AQP1. With reference to the model, the findings also suggest that tight junctional water flux in the PT is less prominent in the mouse than rat kidney.