Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice

J Clin Invest. 1998 Feb 1;101(3):536-42. doi: 10.1172/JCI1720.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldosterone / blood
  • Animals
  • Body Weight
  • Colon / enzymology*
  • Electrolytes / blood
  • Feces
  • Glomerular Filtration Rate
  • H(+)-K(+)-Exchanging ATPase / biosynthesis
  • H(+)-K(+)-Exchanging ATPase / deficiency*
  • H(+)-K(+)-Exchanging ATPase / genetics
  • Kidney / enzymology
  • Kidney / physiology
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • Organ Size
  • Potassium / metabolism*
  • Potassium / urine
  • RNA, Messenger / biosynthesis
  • Sodium / urine


  • Electrolytes
  • RNA, Messenger
  • Aldosterone
  • Sodium
  • H(+)-K(+)-Exchanging ATPase
  • Potassium