Cation specificity and modes of the Na+:CO3(2-):HCO3- cotransporter in renal basolateral membrane vesicles.
The cation specificity and possible exchange modes of the Na+:CO3(2-):HCO3- cotransporter were evaluated by use of basolateral membrane vesicles isolated from rabbit renal cortex. External Li+ inhibited HCO3- gradient-stimulated 22Na uptake, indicating that Li+ interacts with the Na+:CO3(2-):HCO3- cotransporter. No interaction with K+, choline, Rb+, Cs+, or NH4+ could be similarly detected. Imposing an outward Li+ gradient caused quenching of acridine orange fluorescence in the presence but not in the absence of HCO3-, suggesting that Li+:base cotransport takes place via the Na+:CO3(2-):HCO3- cotransporter. Imposing an outward gradient of unlabeled Na+ stimulated the initial rate of 22Na uptake and induced its transient uphill accumulation, indicating Na(+)-Na+ exchange. Na(+)-Na+ exchange was observed in the presence but not in the absence of HCO3- and was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), suggesting that it occurs via the Na+:CO3(2-):HCO3- cotransporter. Similarly, an outward Li+ gradient stimulated uphill 22Na accumulation, indicating Na(+)-Li+ exchange. Na(+)-Li+ exchange was observed in the presence but not in the absence of HCO3-, and was inhibited by DIDS, suggesting that it also occurs via the Na+:CO3(2-):HCO3- cotransporter. Both Na(+)-Na+ and Li(+)-Na+ exchange modes were sensitive to inhibition by harmaline but not by amiloride. We conclude that Li+ is an alternative substrate for the renal Na+:CO3(2-):HCO3- cotransporter. Transport modes of the system include cation:base cotransport and HCO3-dependent cation-cation exchange.
Soleimani
M
M
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
Lesoine
G A
GA
Bergman
J A
JA
Aronson
P S
PS
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; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002254:Carbonates / Q000378:metabolism*; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D006246:Harmaline / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism*; D008094:Lithium / Q000378:metabolism; D008297:Male; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D001639:Bicarbonates; D002254:Carbonates; D002412:Cations; D007476:Ionophores; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C005686:sodium carbonate; D000584:Amiloride; D008094:Lithium; D012964:Sodium; D006246:Harmaline; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid