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

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

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
Volume101
Issue number3
DOIs
StatePublished - Feb 1 1998
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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    Meneton, P., Schultheis, P. J., Greeb, J., Nieman, M. L., Liu, L. H., Clarke, L. L., Duffy, J. J., Doetschman, T., Lorenz, J. N., & Shull, G. E. (1998). Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice. Journal of Clinical Investigation, 101(3), 536-542. https://doi.org/10.1172/JCI1720