Evidence that parallel Na⁺-H⁺ and Cl^--HCO₃ ^-(OH^-) antiporters transport NaCl in the proximal tubule

The present in vitro microperfusion study examined whether active NaCl transport in the proximal convoluted tubule (PCT) occurs via parallel Na⁺-H⁺ and Cl^--HCO₃ ^-(OH^-) exchangers. PCT were perfused with a high chloride, low-bicarbonate solution simulating late proximal tubular fluid, and were bathed in a similar solution containing 6 g/dl albumin. In this setting the driving forces responsible for passive NaCl transport are eliminated. Addition of 0.1 or 0.5 mM luminal 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), 0.5 mM luminal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), or 0.1 mM bath ethoxyzolamide, a lipophilic carbonic anhydrase inhibitor, resulted in an approximately 50% reduction in volume absorption. Inhibition of the Na⁺-H⁺ antiporter with 1.0 mM luminal amiloride inhibited volume absorption by 50%. The transepithelial potential difference (PD) was no significantly different from zero, consistent with an electroneutral mechanism for active NaCl transport. The effect of a Cl^--HCO₃ ^-(OH^-) exchanger on acidification was examined in PCT perfused with an ultrafiltrate-like solution and bathed in a serumlike albumin solution. Addition of 0.5 mM DIDS did not significantly decrease volume absorption, demonstrating that luminal DIDS did not result in a nonspecific decrease in solute transport. Luminal DIDS significantly stimulated bicarbonate absorption, consistent with a Na⁺-H⁺ antiporter running in parallel with a Cl^--HCO₃ ^-(OH^-) antiporter, which exchanges luminal Cl^- for cellular HCO₃ ^- (or OH^-). In conclusion, these data are consistent with parallel Na⁺-H⁺ and Cl^--HCO₃ ^-(OH^-) antiporters mediating neutral active NaCl transport in the PCT.