Ontogeny of Na+/H+ antiporter activity in rat proximal convoluted tubules.
Neonates have a lower serum bicarbonate level than adults, which is caused by a lower renal threshold for bicarbonate. Eighty percent of bicarbonate reabsorption occurs in the proximal tubule, in which proton secretion is predominantly mediated by a luminal Na+/H+ antiporter. Previous studies have demonstrated that there is a maturational increase in apical membrane rabbit proximal convoluted tubule Na+/H+ antiporter activity. However, in rat brush border membrane vesicles, Na+/H+ activity was higher in neonates than that in adult rats. To examine the maturation of Na+/H+ antiporter activity in rat proximal convoluted tubules, we perfused rat proximal convoluted tubules in vitro. Na+/H+ antiporter activity was assayed as the proton secretory rate on luminal sodium removal. Na+/H+ antiporter activity was 121.2 +/- 18.4 pmol/mm x min in neonatal and 451.8 +/- 40.6 pmol/mm x min in adult proximal convoluted tubules (p < 0.001). We next examined whether the increase in Na+/H+ antiporter activity was associated with changes in renal cortical NHE3 mRNA and brush border membrane NHE3 protein abundance. Adult renal cortical NHE3 mRNA abundance was 10-fold greater than that in 1-d-old neonates (p < 0.001). There was a comparable developmental increase in renal brush border membrane vesicle NHE3 protein abundance (p < 0.001). In summary, this study demonstrates that there is a maturational increase in rat apical membrane Na+/H+ antiporter activity, renal cortical NHE3 mRNA, and brush border membrane vesicle NHE3 protein abundance.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
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Shah
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Gupta
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Dwarakanath
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Moe
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Baum
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D018507:Gene Expression Regulation, Developmental; D006863:Hydrogen-Ion Concentration; D007672:Kidney Cortex / Q000502:physiology; D007684:Kidney Tubules / Q000254:growth & development / Q000502:physiology*; D007700:Kinetics; D008871:Microvilli / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic
D012333:RNA, Messenger; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium