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 journalArticle

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Abstract

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)
JournalAmerican Journal of Physiology - Renal Physiology
Volume303
Issue number11
DOIs
StatePublished - Dec 1 2012

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Sodium-Hydrogen Antiporter
Microvilli
Membranes
Kidney
Bicarbonates
Blood Pressure
Acidosis

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Proximal tubule Na+/H+ exchanger activity in adult NHE8-/-, NHE3-/-, and NHE3-/-/NHE8-/- mice. / Baum, Michel; Twombley, Katherine; Gattineni, Jyothsna; Joseph, Catherine; Wang, Lin; Zhang, Qiuyu; Dwarakanath, Vangipuram; Moe, Orson W.

In: American Journal of Physiology - Renal Physiology, Vol. 303, No. 11, 01.12.2012.

Research output: Contribution to journalArticle

Baum, Michel ; Twombley, Katherine ; Gattineni, Jyothsna ; Joseph, Catherine ; Wang, Lin ; Zhang, Qiuyu ; Dwarakanath, Vangipuram ; Moe, Orson W. / Proximal tubule Na+/H+ exchanger activity in adult NHE8-/-, NHE3-/-, and NHE3-/-/NHE8-/- mice. In: American Journal of Physiology - Renal Physiology. 2012 ; Vol. 303, No. 11.
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AU - Wang, Lin

AU - Zhang, Qiuyu

AU - Dwarakanath, Vangipuram

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AB - 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.

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KW - Development

KW - Proximal tubule

KW - Sodium/hydrogen exchanger

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