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 not 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.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D005016:Ethoxzolamide / Q000494:pharmacology; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D011817:Rabbits; D012965:Sodium Chloride / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D017923:Sodium-Hydrogen Exchangers; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D012965:Sodium Chloride; D000584:Amiloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005016:Ethoxzolamide