Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice.
Previous studies using isolated tissues suggest that the colonic H, K-ATPase (cHKA), expressed in the colon and kidney, plays an important role in K+ conservation. To test the role of this pump in K+ homeostasis in vivo, we generated a cHKA-deficient mouse and analyzed its ability to retain K+ when fed a control or K+-free diet. When maintained on a control diet, homozygous mutant (cHKA-/-) mice exhibited no deficit in K+ homeostasis compared to wild-type (cHKA+/+ greater, similar mice. Although fecal K+ excretion in cHKA-/- mice was double that of cHKA+/+ mice, fecal K+ losses were low compared with urinary K+ excretion, which was similar in both groups. When maintained on a K+-free diet for 18 d, urinary K+ excretion dropped over 100-fold, and to similar levels, in both cHKA-/- and cHKA+/+ mice; fecal K+ excretion was reduced in both groups, but losses were fourfold greater in cHKA-/- than in cHKA+/+ mice. Because of the excess loss of K+ in the colon, cHKA-/- mice exhibited lower plasma and muscle K+ than cHKA+/+ mice. In addition, cHKA-/- mice lost twice as much body weight as cHKA+/+ mice. These results demonstrate that, during K+ deprivation, cHKA plays a critical role in the maintenance of K+ homeostasis in vivo.
Meneton
P
P
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Schultheis
P J
PJ
Greeb
J
J
Nieman
M L
ML
Liu
L H
LH
Clarke
L L
LL
Duffy
J J
JJ
Doetschman
T
T
Lorenz
J N
JN
Shull
G E
GE
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001835:Body Weight; D003106:Colon / Q000201:enzymology*; D004573:Electrolytes / Q000097:blood; D005243:Feces; D005919:Glomerular Filtration Rate; D017506:H(+)-K(+)-Exchanging ATPase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D007668:Kidney / Q000201:enzymology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009929:Organ Size; D011188:Potassium / Q000378:metabolism* / Q000652:urine; D012333:RNA, Messenger / Q000096:biosynthesis; D012964:Sodium / Q000652:urine
D004573:Electrolytes; D012333:RNA, Messenger; D000450:Aldosterone; D012964:Sodium; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium