Kidney Week

Abstract: TH-PO342

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

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

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

Authors

• Du, Zhaopeng, Yale School of Medicine, New Haven, Connecticut, United States

Zhaopeng Du,

• Yan, Qingshang, Yale School of Medicine, New Haven, Connecticut, United States

Qingshang Yan,

• Weinstein, Alan Mark, Weill Medical College of Cornell University, New York, New York, United States

Alan Mark Weinstein,

• Wang, Tong, Yale School of Medicine, New Haven, Connecticut, United States

Tong Wang,

Background

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.

Methods

We investigated flow-mediated fluid (J_v) and HCO₃^- (J_HCO3) 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 J_v and J_HCO3 were measured. The experiments were simulated in an adaptation of a mathematical model of rat PT.

Results

An increase in perfusion rate from 5 to 20 nl/min increased J_v by 73% and J_HCO3 by 106% in proximal tubules of WT mice. AQP-1 knockout significantly decreased J_v by 28% and 72% at low and high flow rates respectively compared with WT control. In contrast, the J_HCO3 was not reduced at either low or high flow rates. The fractional increase in J_v by flow was completely abolished, but fractional increase in J_HCO3 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 J_v between WT and KO; whereas TJ Pf set to 25% of rat, predicted J_v concordant with our observations from AQP1 KO.

Conclusion

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.

Funding

• NIDDK Support