Aquaporins by Baoxue Yang

Author:Baoxue Yang
Language: eng
Format: epub
Publisher: Springer Netherlands, Dordrecht

9.2 Functions of AQPs in Urinary System

9.2.1 AQP1

To evaluate the role of AQP1 in the proximal tubule, Verkman’s group generated AQP1 knockout mice by targeted gene disruption [85, 137, 159, 160, 170, 172]. The AQP1 null mice were not obviously different from wild-type mice in survival, gross physical appearance, and organ morphology, except for mild growth retardation.

The measurement of the transepithelial osmotic water permeability (P f) in S2 segments of proximal tubule showed that P f in AQP1 null mice was five-fold lower than that in wild-type mice, which indicates that osmolality driven transcellular water permeability is through AQP1. In purified apical plasma membrane vesicles of proximal tubule, P f (at 10 °C) decreased nine-fold in AQP1 null mice compared with wild-type mice. The remaining low water permeability in AQP1 null proximal tubule was not been inhibited by mercurial agents. Furthermore, an intrinsic membrane P f of approximately 0.006 cm/s (at 37 °C) in AQP1 null proximal tubule, which is similar with water movement exclusively across the lipid portion of the membrane, suggesting that other AQP -type water channel and non-aquaporin transporters play little role in proximal tubule water permeability. Less than 20% of osmotically driven transepithelial water transport in the proximal tubule is paracellular [158].

The higher urine output demonstrates that AQP1 null mice have reduced fluid absorption in the collecting duct. The deletion of AQP1 in the TDLH and DVR likely resulted in a defective countercurrent mechanism, which prevents the formation of a hyperosmolar medullary interstitium. In water -deprived AQP1 null mice, dDAVP stimulation of collecting duct water permeability (that should nearly equalize urinary and medullary interstitial osmolality) did not increase urinary osmolality [15, 85]. Because salt transporters are functional and the collecting duct can be water permeable, AQP1 null mice can mildly concentrate urine.

Ex vivo perfused segments of TDLH were used to study the contribution of AQP1 to TDLH water permeability [19]. P f was significantly lower in AQP1 null TDLH, indicating that the main water channel in TDLH is AQP1, which also reveals that osmotic equilibration along the TDLH mediated by water transport makes contribution to the renal countercurrent concentrating mechanism.

There is a long-standing controversy regarding the relative contributions of water reabsorption and solute entry to osmotic equilibration along the TDLH [103]. AQP1 null mice showed urine-concentrating defect and a decrease in TDLH water permeability indicating that high water permeability in the TDLH plays an important role in urine concentration. AQP1 deletion does not affect the NaCl and urea permeabilities of the TDLH, so that osmotic water transport out of the lumen of the TDLH is important for the countercurrent multiplication mechanism and that solute entry by itself is not sufficient to permit the formation of maximally concentrated urine [158].

Average body weight decreased by 35% in the AQP1 null mice compared with 20~22% in wild-type mice, and blood osmolality increased to 517 mosm/kg H2O compared with 311~325 mosm/kg H2O in wild-type mice after being deprived of water for 36 h. Interestingly, nearly all water-deprived AQP1 null mice

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