Proximal tubule Na+/H+ exchanger activity in adult NHE8-/-, NHE3-/-, and NHE3-/-/NHE8-/- mice.
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.
Dept. of Pediatrics, Univ. of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA. Michel.Baum@UTSouthwestern.edu
Michel
M
Baum
Katherine
K
Twombley
Jyothsna
J
Gattineni
Catherine
C
Joseph
Lin
L
Wang
Qiuyu
Q
Zhang
Vangipuram
V
Dwarakanath
Orson W
OW
Moe
D000138:Acidosis / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D023421:Models, Animal; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
D001639:Bicarbonates; C000613386:Slc9a3 protein, mouse; C471945:Slc9a8 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers