ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2022 and some content may be unavailable. To unlock all content for 2022, please visit the archives.

Abstract: TH-PO342

Regulation of Glomerulotubular Balance IV: Implication of Aquaporin 1 in Flow-Dependent Proximal Tubule Transport and Cell Volume

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

  • 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic


  • Du, Zhaopeng, Yale School of Medicine, New Haven, Connecticut, United States
  • Yan, Qingshang, Yale School of Medicine, New Haven, Connecticut, United States
  • Weinstein, Alan Mark, Weill Medical College of Cornell University, New York, New York, United States
  • Wang, Tong, Yale School of Medicine, New Haven, Connecticut, United States

In proximal tubule (PT), glomerulotubular balance (GTB) derives from the impact of axial flow to regulate Na+ and HCO3- transport by modulating luminal membrane NHE3 and H-ATPase activity with little change of cell volume. The water channel, aquaporin-1 (AQP-1) is the principal water pathway for isotonic water absorption in the kidney proximal tubule.


We investigated flow-mediated fluid (Jv) and HCO3- (JHCO3) absorption in proximal tubules (S2) of mouse kidney by microperfusion in vitro in wild-type (WT) and AQP-1 KO mice. The PTs (S2) were isolated and perfused in vitro under low (5nl/min) and high (20nl/min) perfusion rates and the Jv and JHCO3 were measured. The experiments were simulated in an adaptation of a mathematical model of rat PT.


An increase in perfusion rate from 5 to 20 nl/min increased Jv by 73% and JHCO3 by 106% in proximal tubules of WT mice. AQP-1 knockout significantly decreased Jv by 28% and 72% at low and high flow rates respectively compared with WT control. In contrast, the JHCO3 was not reduced at either low or high flow rates. The fractional increase in Jv by flow was completely abolished, but fractional increase in JHCO3 was not reduced by AQP-1 KO. The cell volume showed no significant difference at either low or high flow rates or between WT and AQP-1 KO mice. In addition, renal clearance experiments showed significantly higher urine flow in KO mouse but there was no significant difference in either Na+ and K+ excretion or HCO3- excretion. The acid-base parameters of blood pH, PCO2, HCO3- and urine pH were the same in both WT and KO mouse. In model calculations, tubules whose tight junction (TJ) Pf was that assigned to rat TJ, showed no difference in Jv between WT and KO; whereas TJ Pf set to 25% of rat, predicted Jv concordant with our observations from AQP1 KO.


These results affirm the dominance of AQP-1 in mediating isotonic water absorption by mouse PT and demonstrate that flow-stimulated HCO3- reabsorption is intact and independent of AQP-1. With reference to the model, the findings also suggest that tight junctional water flux in proximal tubule is less prominent in mouse than in rat kidney.


  • NIDDK Support