The reabsorption of Na+ in the first half of the proximal tubule is mainly facilitated by a Na+/H+ antiporter called NHE3. This process is present in all cells of the proximal tubule but is discussed separately for simplicity. On the apical membrane, the Na+/H+ antiporter operates alongside the Na+,K+-ATPase and HCO3− transporters, including the Na+/HCO3− symporter (NBC1), to promote the reabsorption of NaHCO3. Inside the cells, carbon dioxide and water combine with the help of the enzyme carbonic anhydrase (CA) to form H+ and HCO3−. On the basolateral membrane, the Na+,K+-ATPase, as well as the glucose transporter (GLUT2), work in conjunction with the Na+/glucose symporter (SGLT2) in the apical membrane to facilitate the reabsorption of Na+-glucose. Mutations that deactivate the GLUT2 gene result in reduced glucose reabsorption in the proximal tubule, leading to glucosuria (i.e., glucose in the urine). In addition to glucose, Na+ reabsorption is also coupled with other solutes such as amino acids, Pi, and lactate. These solutes are reabsorbed through the Na+/amino acid, Na+/Pi, and Na+/lactate symporters located in the apical membrane, as well as the Na+,K+-ATPase, amino acid, Pi, and lactate transporters located in the basolateral membrane. The proximal tubule contains three classes of amino acid transporters: two that transport Na+ along with either acidic or basic amino acids, and one that does not require Na+ and transports basic amino acids.
In terms of solute concentration in the tubule fluid along the proximal tubule, values above 100 indicate that less of the solute compared to water is reabsorbed, while values below 100 indicate that more of the substance compared to water is reabsorbed.
Na+ enters the cell across the luminal membrane primarily via the parallel operation of a Na+/H+ antiporter (NHE3) •Fig. 34.1 Na+ transport processes in the first half of the proximal tubule. These transport mechanisms are present in all cells in the first half of the proximal tubule but are separated into different cells to simplify the discussion. A, Operation of the Na+/H+ antiporter (NHE3) in the apical membrane and the Na+,K+-ATPase and HCO3− transporters, including the Na+/HCO3− symporter (NBC1; see also ) in the basolateral membrane mediates reabsorption of NaHCO3. Carbon dioxide and water combine inside the cells to form H+ and HCO3− in a reaction facilitated by the enzyme carbonic anhydrase (CA). B, Operation of the Na+/glucose symporter (SGLT2) in the apical membrane, in conjunction with Na+,K+-ATPase and the glucose transporter (GLUT2) in the basolateral membrane, mediates Na+-glucose reabsorption. Inactivating mutations in the GLUT2 gene lead to decreased glucose reabsorption in the proximal tubule and glucosuria (i.e., glucose in the urine). Though not shown, Na+ reabsorption is also coupled with other solutes, including amino acids, Pi, and lactate. Reabsorption of these solutes is mediated by the Na+/amino acid, Na+/Pi, and Na+/lactate symporters, respectively, located in the apical membrane and the Na+,K+-ATPase, amino acid, Pi, and lactate transporters, respectively, located in the basolateral membrane. Three classes of amino acid transporters have been identified in the proximal tubule: two that transport Na+ in conjunction with either acidic or basic amino acids and one that does not require Na+ and transports basic amino acids.
•Fig. 34.2 Concentration of solutes in tubule fluid as a function of length along the proximal tubule. [TF] is the concentration of the substance in tubular fluid; [P] is the concentration of the substance in plasma.
Values above 100 indicate that relatively less of the solute than water is reabsorbed, and values below 100 indicate that relatively more of the substance than water is reabsorbed.