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

Pierre Meneton, Patrick J. Schultheis, Jeannette Greeb, Michelle L. Nieman, Lynne H. Liu, Lane L. Clarke, John J. Duffy, Thomas Doetschman, John N. Lorenz, Gary E. Shull

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141 Scopus citations


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(+/+) 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.

Original languageEnglish (US)
Pages (from-to)536-542
Number of pages7
JournalJournal of Clinical Investigation
Issue number3
StatePublished - Feb 1 1998


  • Gene targeting
  • K homeostasis colon kidney
  • P-type ATPase

ASJC Scopus subject areas

  • General Medicine


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