Water channels called aquaporins (AQPs) mediate transcellular reabsorption of water across many nephron segments. To date, 13 aquaporins have been identified. The AQP family is divided into two groups based on their permeability characteristics. One group (aquaporins) is permeable to water (AQP0, AQP1, AQP2, AQP4, AQP5, AQP6, AQP8, AQP11, and AQP12). The other group (aquaglyceroporins) is permeable to water and small solutes, especially glycerol (AQP3, AQP7, AQP9, AQP10). Aquaporins form tetramers in the plasma membrane of cells, with each subunit forming a water channel. In the kidneys, AQP1 is expressed in the apical and basolateral membranes of the proximal tubule and in portions of the descending thin limb of Henle’s loop. The importance of AQP1 in renal water reabsorption is underscored by studies in which the AQP1 gene was “knocked out” in mice. These mice exhibit increased urine output (polyuria) and reduced ability to concentrate urine. In addition the osmotic water permeability of the proximal tubule is fivefold less in mice lacking APQ1 than in normal mice. AQP7 and AQP8 are also expressed in the proximal tubule. AQP2 is expressed in the apical plasma membrane of principal cells in the collecting duct, and its abundance in the membrane is regulated by arginine vasopressin (AVP) (see ). AQP3 and AQP4 are expressed in the basolateral membrane of principal cells in the collecting duct, and mice deficient in these AQPs (i.e., AQP3 and AQP4 knockout mice) have defects in the ability to concentrate urine (see ). AQPs are also expressed in many other organs in the body, including the lung, eye, skin, secretory glands, and brain, where they play key physiological roles. For example, AQP4 is expressed in cells that form the blood-brain barrier. Knockout of AQP4 affects the water permeability of the blood-brain barrier such that brain edema is reduced in AQP4-deficient mice after acute water loading and subsequent development of hyponatremia.
ATP ATP ADP ˜-KG NaDC3 OAT 1,2,3 OAT4 OA– ˜-KG MRP2/4 BCRP K+ •Fig. 34.5 Secretion of organic anion (OA−) across the proximal tubule. OA−s enter the cell across the basolateral membrane by one of three OA−/α-ketoglutarate (α-KG) antiporter mechanisms (organic anion transporters, OAT1, OAT2, OAT3). Uptake of α-KG into the cell against its chemical concentration gradient is driven by movement of Na+ into the cell via the Na+-dicarboxylate transporter (NaDC3). The [Na+] inside the cell is low because of the Na+,K+-ATPase in the basolateral membrane, which transports Na+ out of the cell in exchange for K+ . The α-KG recycles across the basolateral membrane on the OATs in exchange for OA− . OA−s leave the cell across the apical membrane by multidrug drug resistance proteins (MRP2 and 4), and by breast cancer resistance protein (BCRP), which require ATP. OAT4 in the apical membrane reabsorbs urate, an organic anion.