Rheogenic sodium-bicarbonate cotransport in the peritubular cell membrane of rat renal proximal tubule

Abstract

The mechanism of bicarbonate transport across the peritubular cell membrane was investigated in rat kidney proximal tubules in situ by measuring cell pH and cell Na+ activity in response to sudden reduction of peritubular Na+ and/or HCO3-. The following observations were made: 1. sudden peritubular reduction of either ion concentration produced the same transient depolarizing potential response; 2. bicarbonate efflux in response to peritubular reduction of bicarbonate was accompanied by sodium efflux; 3. sodium efflux in response to peritubular sodium removal was accompanied by cell acidification indicating bicarbonate efflux; 4. all aforementioned phenomena were inhibited by SITS (10(-3) mol/l) except for a small SITS-independent sodium efflux and depolarization which occurred in response to peritubular sodium removal and was not accompanied by cell pH changes; 5. bicarbonate efflux and accompanying potential changes in response to reduction of peritubular bicarbonate virtually vanished in sodium-free solutions. From these observations we conclude that bicarbonate efflux proceeds as rheogenic sodium-bicarbonate cotransport with a stoichiometry of bicarbonate to sodium greater than 1. The question which of the charged species of the bicarbonate buffer system moves cannot yet be decided. Attempts to determine the stoichiometry from the SITS-inhibitable initial cell depolarization and from the SITS-inhibitable initial fluxes suggest a stoichiometry of 3 HCO3-: 1 Na+. In addition to sodium-dependent bicarbonate flux, evidence was obtained for a sodium-independent transport system of acids or bases which is able to regulate cell pH even in sodium-free solutions.

Regulation of intracellular pH in eukaryotic cells

“…The transporter was postulated to mediate net efflux of HCO3-and Na+, giving rise to transcellular transport of HCO3-. A similar process was described in monkey kidney epithelial cells (Jentsch et al, 1985), and in proximal tubular cells ofthe rat (Alpern, 1985;Yoshitomi et al, 1985) and the rabbit (Biagi & Sohtell, 1986;Sasaki et al, 1985).…”

“…It is still unclear whether different molecular entities are involved in the two kinds of anion antiport. Na+/HCO3-symport A number of authors have recently presented evidence for electrogenic symport of Na+ and HCO3-in a variety of cells involved in transepithelial transport of acid (Boron & Boulpaep, 1983;Alpern, 1985;Jentsch et al, 1985Jentsch et al, , 1986bYoshitomi et al, 1985;Biagi & Sohtell, 1986). This symport has been described to couple tightly the transport of one Na+ ion to two or three HCO3-ions.…”

Molecular Cloning, Chromosomal Localization, Tissue Distribution, and Functional Expression of the Human Pancreatic Sodium Bicarbonate Cotransporter

“…As characterized in many cell types, several features distinguish the Na(HCO 3 ) n cotransporter from other bicarbonate-dependant transporters.1) Na(HCO 3 ) n cotransport is not dependent on the presence of Cl Ϫ , 2) transport is inhibited by stilbenes, and 3) transport is stimulated in the presence of HCO 3 Ϫ . In the kidney, Na(HCO 3 ) n cotransport was initially localized by functional studies to the basolateral membrane of the proximal tubule where it plays an important role in mediating electrogenic basolateral bicarbonate efflux (2,21,22). Although Na ϩ -dependent and -independent Cl Ϫ /base exchangers also contribute to basolateral bicarbonate transport in the proximal tubule (23)(24)(25)(26)(27), current evidence suggests that electrogenic Na(HCO 3 ) n cotransport mediates the majority of bicarbonate efflux in this nephron segment (1).…”

Tubular Effects of Insulin

“…In proximal tubules, Na reabsorption across the brush border membrane depends on Na/H exchange driven by an electrochemical gradient created by Na/KATPase (5). Renal acidification in this segment is mediated mainly by Na/H exchange in the luminal membrane and Na-HCO3 cotransporter in the basolateral membrane (6,7). Na and HCO3 reabsorptions are mainly accomplished by active transport, which involves Na/H exchange.…”