Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1998 Feb 1;101(3):536–542. doi: 10.1172/JCI1720

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

P Meneton 1, P J Schultheis 1, J Greeb 1, M L Nieman 1, L H Liu 1, L L Clarke 1, J J Duffy 1, T Doetschman 1, J N Lorenz 1, G E Shull 1
PMCID: PMC508595  PMID: 9449685

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+/+ 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.

Full Text

The Full Text of this article is available as a PDF (488.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahn K. Y., Park K. Y., Kim K. K., Kone B. C. Chronic hypokalemia enhances expression of the H(+)-K(+)-ATPase alpha 2-subunit gene in renal medulla. Am J Physiol. 1996 Aug;271(2 Pt 2):F314–F321. doi: 10.1152/ajprenal.1996.271.2.F314. [DOI] [PubMed] [Google Scholar]
  2. Buffin-Meyer B., Younes-Ibrahim M., Barlet-Bas C., Cheval L., Marsy S., Doucet A. K depletion modifies the properties of Sch-28080-sensitive K-ATPase in rat collecting duct. Am J Physiol. 1997 Jan;272(1 Pt 2):F124–F131. doi: 10.1152/ajprenal.1997.272.1.F124. [DOI] [PubMed] [Google Scholar]
  3. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Codina J., Kone B. C., Delmas-Mata J. T., DuBose T. D., Jr Functional expression of the colonic H+,K+-ATPase alpha-subunit. Pharmacologic properties and assembly with X+,K+-ATPase beta-subunits. J Biol Chem. 1996 Nov 22;271(47):29759–29763. doi: 10.1074/jbc.271.47.29759. [DOI] [PubMed] [Google Scholar]
  5. Codina J., Pressley T. A., DuBose T. D., Jr Effect of chronic hypokalemia on H(+)-K(+)-ATPase expression in rat colon. Am J Physiol. 1997 Jan;272(1 Pt 2):F22–F30. doi: 10.1152/ajprenal.1997.272.1.F22. [DOI] [PubMed] [Google Scholar]
  6. Cougnon M., Planelles G., Crowson M. S., Shull G. E., Rossier B. C., Jaisser F. The rat distal colon P-ATPase alpha subunit encodes a ouabain-sensitive H+, K+-ATPase. J Biol Chem. 1996 Mar 29;271(13):7277–7280. doi: 10.1074/jbc.271.13.7277. [DOI] [PubMed] [Google Scholar]
  7. Crowson M. S., Shull G. E. Isolation and characterization of a cDNA encoding the putative distal colon H+,K(+)-ATPase. Similarity of deduced amino acid sequence to gastric H+,K(+)-ATPase and Na+,K(+)-ATPase and mRNA expression in distal colon, kidney, and uterus. J Biol Chem. 1992 Jul 5;267(19):13740–13748. [PubMed] [Google Scholar]
  8. Del Castillo J. R., Rajendran V. M., Binder H. J. Apical membrane localization of ouabain-sensitive K(+)-activated ATPase activities in rat distal colon. Am J Physiol. 1991 Dec;261(6 Pt 1):G1005–G1011. doi: 10.1152/ajpgi.1991.261.6.G1005. [DOI] [PubMed] [Google Scholar]
  9. Doucet A., Marsy S. Characterization of K-ATPase activity in distal nephron: stimulation by potassium depletion. Am J Physiol. 1987 Sep;253(3 Pt 2):F418–F423. doi: 10.1152/ajprenal.1987.253.3.F418. [DOI] [PubMed] [Google Scholar]
  10. DuBose T. D., Jr, Codina J., Burges A., Pressley T. A. Regulation of H(+)-K(+)-ATPase expression in kidney. Am J Physiol. 1995 Oct;269(4 Pt 2):F500–F507. doi: 10.1152/ajprenal.1995.269.4.F500. [DOI] [PubMed] [Google Scholar]
  11. DuBose T. D., Jr, Codina J. H,K-ATPase. Curr Opin Nephrol Hypertens. 1996 Sep;5(5):411–416. doi: 10.1097/00041552-199609000-00006. [DOI] [PubMed] [Google Scholar]
  12. Elger M., Bankir L., Kriz W. Morphometric analysis of kidney hypertrophy in rats after chronic potassium depletion. Am J Physiol. 1992 Apr;262(4 Pt 2):F656–F667. doi: 10.1152/ajprenal.1992.262.4.F656. [DOI] [PubMed] [Google Scholar]
  13. Foster E. S., Hayslett J. P., Binder H. J. Mechanism of active potassium absorption and secretion in the rat colon. Am J Physiol. 1984 May;246(5 Pt 1):G611–G617. doi: 10.1152/ajpgi.1984.246.5.G611. [DOI] [PubMed] [Google Scholar]
  14. Foster E. S., Jones W. J., Hayslett J. P., Binder H. J. Role of aldosterone and dietary potassium in potassium adaptation in the distal colon of the rat. Gastroenterology. 1985 Jan;88(1 Pt 1):41–46. doi: 10.1016/s0016-5085(85)80130-x. [DOI] [PubMed] [Google Scholar]
  15. Garg L. C., Narang N. Ouabain-insensitive K-adenosine triphosphatase in distal nephron segments of the rabbit. J Clin Invest. 1988 Apr;81(4):1204–1208. doi: 10.1172/JCI113436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Imbert-Teboul M., Doucet A., Marsy S., Siaume-Perez S. Alterations of enzymatic activities along rat collecting tubule in potassium depletion. Am J Physiol. 1987 Sep;253(3 Pt 2):F408–F417. doi: 10.1152/ajprenal.1987.253.3.F408. [DOI] [PubMed] [Google Scholar]
  17. Jaisser F., Coutry N., Farman N., Binder H. J., Rossier B. C. A putative H(+)-K(+)-ATPase is selectively expressed in surface epithelial cells of rat distal colon. Am J Physiol. 1993 Oct;265(4 Pt 1):C1080–C1089. doi: 10.1152/ajpcell.1993.265.4.C1080. [DOI] [PubMed] [Google Scholar]
  18. Jaisser F., Escoubet B., Coutry N., Eugene E., Bonvalet J. P., Farman N. Differential regulation of putative K(+)-ATPase by low-K+ diet and corticosteroids in rat distal colon and kidney. Am J Physiol. 1996 Feb;270(2 Pt 1):C679–C687. doi: 10.1152/ajpcell.1996.270.2.C679. [DOI] [PubMed] [Google Scholar]
  19. Kone B. C. Renal H,K-ATPase: structure, function and regulation. Miner Electrolyte Metab. 1996;22(5-6):349–365. [PubMed] [Google Scholar]
  20. Lee J., Rajendran V. M., Mann A. S., Kashgarian M., Binder H. J. Functional expression and segmental localization of rat colonic K-adenosine triphosphatase. J Clin Invest. 1995 Oct;96(4):2002–2008. doi: 10.1172/JCI118247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Marsy S., Elalouf J. M., Doucet A. Quantitative RT-PCR analysis of mRNAs encoding a colonic putative H, K-ATPase alpha subunit along the rat nephron: effect of K+ depletion. Pflugers Arch. 1996 Jul;432(3):494–500. doi: 10.1007/s004240050161. [DOI] [PubMed] [Google Scholar]
  22. Mathews P. M., Claeys D., Jaisser F., Geering K., Horisberger J. D., Kraehenbuhl J. P., Rossier B. C. Primary structure and functional expression of the mouse and frog alpha-subunit of the gastric H(+)-K(+)-ATPase. Am J Physiol. 1995 May;268(5 Pt 1):C1207–C1214. doi: 10.1152/ajpcell.1995.268.5.C1207. [DOI] [PubMed] [Google Scholar]
  23. Okusa M. D., Unwin R. J., Velázquez H., Giebisch G., Wright F. S. Active potassium absorption by the renal distal tubule. Am J Physiol. 1992 Mar;262(3 Pt 2):F488–F493. doi: 10.1152/ajprenal.1992.262.3.F488. [DOI] [PubMed] [Google Scholar]
  24. Sangan P., Rajendran V. M., Mann A. S., Kashgarian M., Binder H. J. Regulation of colonic H-K-ATPase in large intestine and kidney by dietary Na depletion and dietary K depletion. Am J Physiol. 1997 Feb;272(2 Pt 1):C685–C696. doi: 10.1152/ajpcell.1997.272.2.C685. [DOI] [PubMed] [Google Scholar]
  25. Shull G. E., Lingrel J. B. Molecular cloning of the rat stomach (H+ + K+)-ATPase. J Biol Chem. 1986 Dec 25;261(36):16788–16791. [PubMed] [Google Scholar]
  26. Suzuki Y., Kaneko K. Ouabain-sensitive H+-K+ exchange mechanism in the apical membrane of guinea pig colon. Am J Physiol. 1989 Jun;256(6 Pt 1):G979–G988. doi: 10.1152/ajpgi.1989.256.6.G979. [DOI] [PubMed] [Google Scholar]
  27. Tabuchi Y., Takeguchi M., Asano S., Takeguchi N. Ouabain-insensitive, vanadate-sensitive K(+)-ATPase of rat distal colon is partly similar to gastric H+,K(+)-ATPase. Jpn J Physiol. 1992;42(4):577–589. doi: 10.2170/jjphysiol.42.577. [DOI] [PubMed] [Google Scholar]
  28. Tannen R. L. Effect of potassium on renal acidification and acid-base homeostasis. Semin Nephrol. 1987 Sep;7(3):263–273. [PubMed] [Google Scholar]
  29. Wingo C. S. Active proton secretion and potassium absorption in the rabbit outer medullary collecting duct. Functional evidence for proton-potassium-activated adenosine triphosphatase. J Clin Invest. 1989 Jul;84(1):361–365. doi: 10.1172/JCI114165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wingo C. S., Smolka A. J. Function and structure of H-K-ATPase in the kidney. Am J Physiol. 1995 Jul;269(1 Pt 2):F1–16. doi: 10.1152/ajprenal.1995.269.1.F1. [DOI] [PubMed] [Google Scholar]
  31. Zhou X., Wingo C. S. H-K-ATPase enhancement of Rb efflux by cortical collecting duct. Am J Physiol. 1992 Jul;263(1 Pt 2):F43–F48. doi: 10.1152/ajprenal.1992.263.1.F43. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES