REGULATION OF GLOMERULOTUBULAR BALANCE IV: IMPLICATION OF AQUAPORIN 1 IN FLOW‐DEPENDENT TRANSPORT AND CELL VOLUME

Abstract

Underlying glomerulortubular balance (GTB) is the impact of axial flow to regulate Na+ and HCO3− transport by modulating luminal NHE3 and H‐ATPase, and presumably other peritubular transporters, since there is little flow‐dependent change in cell volume. Aquaporin (AQP‐1) serves as a water channel and is the principal water pathway for luminal and peritubular membranes of 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. Perfusion Tubule No. Jv (nl/min/mm) JHCO3 (pmol/min/mm) Cell Volume (μm3) (nl/min) WT KO WT KO WT KO WT KO 5 31 9 0.79±0.04 0.57±0.06† 56.3±3.1 61±5.9 1027 1034 20 10 18 1.37±0.06* 0.38±0.03*† 116±7.5* 133±7.8* 1001 946 P<0.05 compared from low flow rate; P<0.05 compared between WT and KO at same flow rate. 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 (P<0.001). Compared with WT, AQP‐1 KO significantly decreased Jv at both low and high flow rates (P<0.05), and there was actually a decrease in volume flux in the transition from low to high flow (P<0.05). In contrast, the AQP‐1 KO mice showed no difference from WT in JHCO3 at either low or high flow rates. Cell volume showed no significant difference between either low or high flow rates or between WT and AQP‐1 KO mice. These results confirm the role of AQP‐1 as the principal pathway for water reabsorption in proximal tubule. The decrease in Jv with increasing perfusion rate is consistent with a model in which proximal Na+ reabsorption produces a transepithelial osmotic gradient, which then drives volume reabsorption. Whether axial flow increases AQP‐1 activity, remains uncertain. Flow‐stimulated Na+ and HCO3− absorption is independent of intact AQP‐1.