TY - JOUR
T1 - Proximal tubule Na+/H+ exchanger activity in adult NHE8-/-, NHE3-/-, and NHE3-/-/NHE8-/- mice
AU - Baum, Michel
AU - Twombley, Katherine
AU - Gattineni, Jyothsna
AU - Joseph, Catherine
AU - Wang, Lin
AU - Zhang, Qiuyu
AU - Dwarakanath, Vangipuram
AU - Moe, Orson W.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
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.
KW - Acidosis
KW - Development
KW - Proximal tubule
KW - Sodium/hydrogen exchanger
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U2 - 10.1152/ajprenal.00415.2012
DO - 10.1152/ajprenal.00415.2012
M3 - Article
C2 - 23054255
AN - SCOPUS:84870502868
SN - 1931-857X
VL - 303
SP - F1495-F1502
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 11
ER -