Proximal and distal convoluted tubule The site of action of acetazolamide is the proximal convoluted tubule and the site of action of the thiazides is the distal convoluted tubule. The distal nephron has a negative luminal potential because it is poorly permeable to negatively charged ions. Therefore, when Na+ is reabsorbed, negatively charged ions, primarily Cl-, lag behind, producing a negative intraluminal potential. Although a similar situation occurs in the proximal tubule, the proximal tubule has a higher permeability to Cl- and, therefore, does not develop as large a negative intraluminal potential. The distal nephron is less permeable to hydrogen than the proximal tubule. Aldosterone increases Na+ reabsorption from the distal nephron but has no effect on the proximal tubule. K+ is reabsorbed from the proximal tubule and secreted by the distal nephron. Although the amount of H+ excreted each day is determined by the amount of H+ secreted into the distal nephron, Proximal tubule secretes much more H+ than the distal nephron. However, almost all of the H+ secreted in the proximal tubule is reabsorbed in association with the reabsorption of HCO3-