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1 Pediatrics, UT Southwestern, Dallas, Texas, United States
2 Division of Nephrology, University of Texas Southwestern Med Ctr, Dallas, Texas, United States
3 Internal Medicine, Yale university, NewHaven, Connecticut, United States
4 Department of Medicine/Nephrology, Yale School of Medicine, New Haven, Connecticut, United States
* To whom correspondence should be addressed. E-mail: michel.baum{at}utsouthwestern.edu.
Proximal tubule bicarbonate reabsorption is primarily mediated via the Na+/H+ exchanger, identified as NHE3 in adults. Previous studies have demonstrated a maturational increase in rat proximal tubule NHE3 expression with a paucity of NHE3 expression in neonates despite significant sodium-dependent proton secretion. Recently, a novel Na+/H+ antiporter (NHE8) was identified and found to be expressed on the apical membrane of the proximal tubule. To determine if NHE8 may be the antiporter responsible for proton secretion in neonates, the present study characterized the developmental expression of NHE8 in rat proximal tubules. RNA blots and real time RT-PCR demonstrated no developmental difference in the mRNA of renal NHE8. Immunoblots, however, demonstrated peak protein abundance of NHE8 in brush border membrane vesicles (BBMV) of 7 and 14 day old rats compared with expression in the adult rat BBMV. In contrast, adults had a relatively higher level of NHE8 expression in total cortical membrane protein compared to neonates. Immunohistochemistry confirmed the presence of NHE8 on the apical membrane of the proximal tubules of neonatal and adult rats. These data demonstrate that NHE8 does undergo maturational changes on the apical membrane of the rat proximal tubule and may account for the sodium-dependent proton flux seen in neonatal proximal tubules.
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