Aquaporins (AQPs) are water channels that facilitate the transport of water across various segments of the nephron. There are currently 13 identified aquaporins, which are divided into two groups based on their permeability characteristics. One group, called aquaporins, allows the passage of water (AQP0, AQP1, AQP2, AQP4, AQP5, AQP6, AQP8, AQP11, and AQP12). The other group, known as aquaglyceroporins, permits the movement of water and small solutes, particularly glycerol (AQP3, AQP7, AQP9, AQP10). In cells' plasma membrane, aquaporins form tetramers, with each subunit functioning as a water channel.

In the kidneys, AQP1 is present in the apical and basolateral membranes of the proximal tubule and certain portions of the descending thin limb of Henle's loop. The significance of AQP1 in renal water reabsorption is demonstrated in studies involving mice where the AQP1 gene was "knocked out." These mice exhibit increased urine output (polyuria) and a reduced ability to concentrate urine. Moreover, the osmotic water permeability of the proximal tubule is five times lower in mice lacking AQP1 compared to normal mice. AQP7 and AQP8 are also found in the proximal tubule.

AQP2 is located in the apical plasma membrane of principal cells in the collecting duct and its presence is regulated by arginine vasopressin (AVP). AQP3 and AQP4, on the other hand, are expressed in the basolateral membrane of principal cells in the collecting duct. Mice deficient in AQP3 and AQP4 (AQP3 and AQP4 knockout mice) display impaired urine concentration ability. Aquaporins are not only found in the kidneys but also in other organs such as the lung, eye, skin, secretory glands, and brain, where they play vital physiological roles. For instance, AQP4 is present in the cells that form the blood-brain barrier. Knocking out AQP4 affects the water permeability of the blood-brain barrier, resulting in reduced brain edema in AQP4-deficient mice after acute water loading and the subsequent development of hyponatremia.

Figure 34.5 illustrates the secretion of organic anions (OA−) across the proximal tubule. The basolateral membrane facilitates the entry of OA−s through three different mechanisms of organic anion transporters (OAT1, OAT2, OAT3) in exchange for α-ketoglutarate (α-KG). The uptake of α-KG into the cell, against its chemical concentration gradient, is driven by the movement of Na+ through the Na+-dicarboxylate transporter (NaDC3). The low intracellular concentration of Na+ is maintained by the Na+,K+-ATPase in the basolateral membrane, which transports Na+ out of the cell and K+ into the cell. The α-KG is recycled across the basolateral membrane using the OATs in exchange for OA−. The apical membrane allows the exit of OA−s through multidrug resistance proteins (MRP2 and 4) and breast cancer resistance protein (BCRP), which require ATP. Additionally, OAT4 in the apical membrane facilitates the reabsorption of urate, an organic anion.
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.