The thin ascending limb reabsorbs NaCl by a passive mechanism. Reabsorption of water, but not NaCl, in the descending thin limb increases [NaCl] in the tubule fluid entering the ascending thin limb. As the NaCl-rich fluid moves toward the cortex, NaCl diffuses out of the tubule lumen across the ascending thin limb and into the medullary interstitial fluid, down a concentration gradient directed from the tubule fluid to the interstitium (see for details).
The key element in reabsorption of solute by the thick ascending limb is Na+,K+-ATPase in the basolateral membrane (Fig. 34.7 ). As with reabsorption in the proximal tubule, reabsorption of every solute by the thick ascending limb is linked to Na+,K+-ATPase activity. This transporter maintains a low intracellular [Na+], which provides a favorable chemical gradient for the movement of Na+ from tubular fluid into the cell. This movement of Na+ across the apical membrane into the cell is mediated by the 1Na+/1K+/2Cl− symporter (NKCC2), which couples the movement of 1Na+ with 1K+ and 2Cl− . Using the potential energy released by the downhill movement of Na+ and Cl− , this symporter drives the uphill movement of K+ into the cell. K+ channels (ROMK and Maxi-K) in the apical plasma membrane play an important role in reabsorption of NaCl by the thick ascending limb. These K+ channels allow the K+ transported into the cell via the 1Na+/1K+/2Cl− symporter to recycle back into tubule fluid. Because the [K+] in tubule fluid is relatively low, K+ recycling is required for continued operation of the 1Na+/1K+/2Cl− symporter. A Na+/H+ anti-porter (NHE3) in the apical cell membrane also mediates Na+ reabsorption as well as H+ secretion (HCO3 − reabsorption) in the thick ascending limb (see also ). The operation of the Na+/H+ antiporter in the apical membrane results in cellular uptake of Na+ in exchange for H+ . The production of H+ inside cells generates HCO3 −, which exits the cell across the basolateral membrane via a Cl−/HCO3 − antiporter (AE2). Na+ leaves the cell across the basolateral membrane via the Na+,K+-ATPase, whereas K+ and Cl− leave the cell via separate pathways in the basolateral membrane (i.e., K+ and Cl− channels and the K+/Cl− symporter).
614 SECTION7Berne & Levy Physiology •Fig. 34.8 Transport mechanism for NaCl reabsorption in the early segment of the distal tubule. This segment is impermeable to water. Mutations in the apical membrane NaCl symporter (NCC) cause Gitelman syndrome. ATP H2O NCC Na+ K+ K+ K+ Na+ Cl– Blood Tubular fluid Cl–
The voltage across the thick ascending limb is important for reabsorption of several cations. The tubular fluid is positively charged relative to blood because of the unique location of transport proteins in the apical and basolateral membranes. Two points are important: (1) increased NaCl transport by the thick ascending limb increases the magnitude of the positive voltage in the lumen, and (2) this voltage is an important driving force for reabsorption of several cations, including Na+ , K+ , Mg++ , and Ca++ , across the paracellular pathway (see
Fig. 34.7 ). The importance of the paracellular pathway to solute reabsorption is underscored by the observation that inactivating mutations of the tight junction protein claudin-16 reduce reabsorption of Mg++ and Ca++ by the ascending thick limb, even in the presence of a lumen positive transepithelial voltage.