A. Reduced water permeability in an epithelium, such as salivary gland, impairs active, near-isosmolar fluid transport by slowing osmotic water transport into the acinar lumen, resulting in the secretion of a reduced volume of a hypertonic fluid. B. Reduced transepithelial water permeability in kidney collecting duct impairs urinary concentrating ability by preventing osmotic equilibration of luminal fluid. C. Proposed mechanism of AQP-facilitated cell migration, showing water entry into protruding lamellipodia in migrating cells. D. AQP4-dependent neuroexcitation, showing AQP4-facilitated water transport in glial cells, which communicate with neurons through changes in extracellular space volume and K⁺ concentration. E. Reduced steady-state glycerol content in epidermis and stratum corneum in skin in AQP3 deficiency, accounting for reduced skin hydration. F. Proposed mechanism of AQP3-facilitated cell proliferation involving reduced cellular glycerol and consequent reduced ATP energy and biosynthesis. G. Proposed mechanism for adipocyte hypertrophy in AQP7 deficiency, in which impaired AQP7-dependent glycerol escape from adipocytes results in cellular glycerol accumulation and increased triglyceride content. See text for further explanations.

A. Schematic of measurement method showing the introduction of a fluid-filled microneedle into the anterior chamber through the cornea. In calibration studies, a second micropipette connected to a fluid-filled manometer is inserted (left, shown in gray). B. IOP measurements in wildtype, AQP1 and AQP4 null mice, and AQP1/AQP4 double knockout mice showing data in individual eyes (filled circles) and mean ± SE (open circles). * P < 0.05, ** P < 0.002. (bottom) Stability of IOP measurement in wildtype mouse after microneedle insertion. C. Pulsed infusion method to measure aqueous fluid outflow. (inset) Continuous IOP recording in response to 0.1 µl fluid infusion every minute. The fluid infusions produced a rapid increase in IOP (related to anterior chamber compliance) followed by a pressure-dependent decline due to outflow. D. (top) Aqueous fluid production determined from the kinetics of fluorescein disappearance from anterior chamber fluid after transcorneal iontophoresis. (bottom) Aqueous fluid production, shown as half-times (t_1/2) for fluorescein disappearance. *, P < 0.05. Adapted from Zhang and Verkman (2002).

A. AQP1 protein expression (red) in anterior epithelial cells of lens in wildtype mouse. Nuclei stained blue. White box shows magnified area. B. In vitro cataract induction by incubation with high-glucose solution. (left) Diagram of apparatus used to quantify lens transparency, showing isolated lens in saline on a metal grid, illuminated from below. (right) Grid images transmitted through lenses from 4 wildtype and 4 AQP1 mice after 18 h incubation in high-glucose solutions. C. In vivo cataract induction by acetominophen. Photographs taken 4 h of acetaminophen. Adapted from Ruiz-Ederra and Verkman (2006a).

A. (left panel) Colocalization of Kir4.1 (green) and AQP4 (red) in isolated Müller cells from wildtype (+/+, top) and AQP4 null (−/−, bottom) mice, with nuclei stained with DAPI (blue). A, apical end; S, soma; EF, endfoot. (two right panels) Retinal sections from mice. ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer; ILM, inner limiting membrane. B. Spatially resolved Kir4.1 K⁺ conductance in Müller cells. (left) Phase-contrast micrograph showing Müller cell with soma puncture and K⁺ injection micropipette positioned where indicated by white arrows. Endfoot at the top and apical end at the bottom. (right) Representative whole-cell current recordings (voltage −80 mV) before and following pulsed injections of 50 mM K⁺ solution for wildtype (left) and AQP4 null (right) Müller cells. C. Mean current-voltage (I–V) curves of whole-cell currents in Müller cells. D. Single-channel patch-clamp of Kir4.1 K⁺ channels with unitary current-voltage data. Inset shows representative single-channel current traces from cell-attached membrane patches with 145 mM K⁺ in the pipette at −60 mV. Adapted from Ruiz-Ederra et al. (2007).

A. Hematoxylin and eosin-stained retinal sections before and at 12 and 96 hours after 60 min retinal ischemia in wildtype and AQP4 null mice. Note retinal swelling at 12 h and degeneration at 96 h. B. Functional analysis by electroretinography. Representative electroretinograms before and at 1, 2 and 4 days after 45 min retinal ischemia. Adapted from Da and Verkman (2004).

A. AQP3 protein expression in mouse cornea. B. AQP3-dependent corneal re-epithelialization following wounding. (top) An epithelial defect (diameter 2.3 mm) was created at the center of corneas, and resurfacing was followed by fluorescein staining. (bottom) Percent of surface defect healed at 12, 18 and 24 h. C. AQP3-dependent corneal epithelial cell migration. Percent of wound resurfaced in organ culture. Eyes were enucleated after corneal scraping and incubated in medium containing serum. D. AQP3-dependent corneal epithelial cell proliferation. (top) Mid-peripheral cornea showing BrdU-immunoreactive cells (dark brown nuclei) before and at 24 or 48 h after corneal scraping. (bottom) Number of BrdU-positive cells in non-injured cornea (baseline) and during healing (SE, * p < 0.01). Adapted from Levin and Verkman (2006).

A. Reduced thickness in AQP1-deficient adult mouse corneas in paraffin-embedded central corneal sections. Bar, 50 µm. B. Osmotic water transport across the corneal endothelium. (top) Schematic showing micropipette placement for anterior chamber perfusion. (bottom) Time course of corneal thickness following corneal endothelial exposure to hypotonic saline in wildtype (open circles) and AQP1 null (filled circles) mice. C. Restoration of corneal thickness after osmotic swelling. (top) Transient exposure of the corneal surface to hypotonic saline to induce corneal swelling and follow recovery of thickness. (bottom) Time course of corneal thickness, measured in vivo by z-scanning confocal microscopy, following exposure of the corneal surface to hypotonic saline. Adapted from Thiagarajah and Verkman (2002).