SLC12A3 and Gitelman syndrome: The v-H+-ATPase activity of A-IC is facilitated by the increased luminal negativity in CCD (17,36) due to higher Na+ reabsorption by ENaC, and consequently, there is an increase in HCO3- regeneration, which contributes to the metabolic alkalosis observed during chronic use of NCC inhibitors or in Gitelman syndrome (Figure 4).