Proximal tubule Na+/H+ exchanger activity in adult NHE8-/-, NHE3-/-, and NHE3-/-/NHE8-/- mice

Michel Baum, Katherine Twombley, Jyothsna Gattineni, Catherine Joseph, Lin Wang, Qiuyu Zhang, Vangipuram Dwarakanath, Orson W. Moe

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


NHE3 is the predominant Na+/H+ exchanger on the brush-border membrane (BBM) of the proximal tubule in adults. However, NHE3 null mice still have significant renal BBM Na+/H+ activity. NHE8 has been localized to the BBM of proximal tubules and is more highly expressed in neonates than adult animals. The relative role of NHE8 in adult renal H+ transport is unclear. This study examined whether there was compensation by NHE8 in NHE3-/- mice and by NHE3 in NHE8-/- mice. NHE3-/- mice had significant metabolic acidosis, and renal BBM NHE8 protein abundance was greater in NHE3-/- mice than control mice, indicating that there may be compensation by NHE8 in NHE3-/- mice. NHE8-/- mice had serum bicarbonate levels and pH that were not different from controls. NHE3 protein expression on the BBM was greater in NHE8-/- mice than in wild-type mice, indicating that there may be compensation by NHE3 in NHE8-/- mice. Both BBM NHE3 and NHE8 protein abundance increased in response to acidosis. Blood pressure and Na+/H+ exchanger activity were comparable in NHE8-/- mice to that of controls, but both were significantly lower in NHE3-/- mice compared with control mice. Compared with NHE3-/- mice, NHE3-/-/ NHE8-/- mice had lower blood pressures. While serum bicarbonate was comparable in NHE3-/- mice and NHE3-/-/NHE8-/- mice, proximal tubule Na+/H+ exchange activity was less in NHE3-/-/ NHE8-/- mice compared with NHE3-/- mice. In conclusion, NHE3 is the predominant Na+/H+ exchanger in adult mice. NHE8 may play a compensatory role in renal acidification and blood pressure regulation in NHE3-/- mice.

Original languageEnglish (US)
Pages (from-to)F1495-F1502
JournalAmerican Journal of Physiology - Renal Physiology
Issue number11
StatePublished - Dec 1 2012


  • Acidosis
  • Development
  • Proximal tubule
  • Sodium/hydrogen exchanger

ASJC Scopus subject areas

  • Physiology
  • Urology


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