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 C Doetschman, John N. Lorenz, Gary E. Shull

Research output: Contribution to journalArticle

116 Citations (Scopus)

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
StatePublished - Feb 1 1998
Externally publishedYes

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Proton-Translocating ATPases
Homeostasis
Diet
Colon

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Meneton, P., Schultheis, P. J., Greeb, J., Nieman, M. L., Liu, L. H., Clarke, L. L., ... Shull, G. E. (1998). Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice. Journal of Clinical Investigation, 101(3), 536-542.

Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice. / Meneton, Pierre; Schultheis, Patrick J.; Greeb, Jeannette; Nieman, Michelle L.; Liu, Lynne H.; Clarke, Lane L.; Duffy, John J.; Doetschman, Thomas C; Lorenz, John N.; Shull, Gary E.

In: Journal of Clinical Investigation, Vol. 101, No. 3, 01.02.1998, p. 536-542.

Research output: Contribution to journalArticle

Meneton, P, Schultheis, PJ, Greeb, J, Nieman, ML, Liu, LH, Clarke, LL, Duffy, JJ, Doetschman, TC, Lorenz, JN & Shull, GE 1998, 'Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice', Journal of Clinical Investigation, vol. 101, no. 3, pp. 536-542.
Meneton P, Schultheis PJ, Greeb J, Nieman ML, Liu LH, Clarke LL et al. Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice. Journal of Clinical Investigation. 1998 Feb 1;101(3):536-542.
Meneton, Pierre ; Schultheis, Patrick J. ; Greeb, Jeannette ; Nieman, Michelle L. ; Liu, Lynne H. ; Clarke, Lane L. ; Duffy, John J. ; Doetschman, Thomas C ; Lorenz, John N. ; Shull, Gary E. / Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice. In: Journal of Clinical Investigation. 1998 ; Vol. 101, No. 3. pp. 536-542.
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