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·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 dance. 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.