Proximal tubule NaCl reabsorption. Proximal tubule NaCl reabsorption. Unlike the thick ascending limb or distal convoluted tubule, there are no dedicated “NaCl” transporters in the proximal tubule. The proximal tubule uses parallel arrays of symporters and antiporters to affect NaCl entry. (A) Parallel Na+/H+ exchange (NHE3) and Cl−/base− exchange (CFEX, SLC26A6) with recycling of the conjugate acid HX resulting in net NaCl entry. (B) A triple coupling mechanism where Na-sulfate cotransport (NaS-1) runs in parallel with two anion exchangers to achieve NaCl cotransport. (C) Na+-coupled organic solute transport with concurrent paracellular Cl− transport driven by the lumen-to-interstitial space downhill chemical gradient of [Cl−]. Basolateral Na+ exit is mediated by the Na+/K+-ATPase but some Na+ also exit with HCO3− (see Figure 3). Cl− exit is less well defined utilizing a variety of transporters and possibly a Cl− channel. Norman P. Curthoys, and Orson W. Moe CJASN 2014;9:1627-1638 ©2014 by American Society of Nephrology