Abstract
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·min in neonatal and 451.8 ± 40.6 pmol/mm·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.
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Abbreviations
- NHE:
-
sodium hydrogen exchanger
- pHi:
-
intracellular pH
- BBMV:
-
brush border membrane vesicles
- EIPA:
-
5-(N-ethyl-N-isopropyl)-amiloride
- BCECF:
-
2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein
- JH:
-
proton secretory rate
- PCT:
-
proximal convoluted tubule
- NaOAc:
-
sodium acetate
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The authors thank Janell McQuinn for her secretarial assistance.
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Supported by National Institutes of Health grants DK41612 (M.B.) and DK48482 and the Department of Veteran Affairs Research Service (O.W.M.).
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Shah, M., Gupta, N., Dwarakanath, V. et al. Ontogeny of Na+/H+ Antiporter Activity in Rat Proximal Convoluted Tubules. Pediatr Res 48, 206–210 (2000). https://doi.org/10.1203/00006450-200008000-00014
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DOI: https://doi.org/10.1203/00006450-200008000-00014
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