HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.

Abstract
Prolonged hypokalemia causes vasopressin-resistant polyuria. We have recently shown that another cause of severe polyuria, chronic lithium therapy, is associated with decreased aquaporin-2 (AQP2) water channel expression (Marples, D., S. Christensen, E.I. Christensen, P.D. Ottosen, and S. Nielsen, 1995. J. Clin. Invest., 95: 1838-1845). Consequently, we studied the effect in rats of 11 days' potassium deprivation on urine production and AQP2 expression and distribution. Membrane fractions were prepared from one kidney, while the contralateral kidney was perfusion-fixed for immunocytochemistry. Immunoblotting and densitometry revealed a decrease in AQP2 levels to 27+/-3.4% of control levels (n=11, P<0.001) in inner medulla, and 34+/-15% of controls (n=5, P<0.05) in cortex. Urine production increased in parallel, from 11+/-1.4 to 30+/-4.4 ml/day (n=11, P<0.01). After return to a potassium-containing diet both urine output and AQP2 labels normalized within 7 d. Immunocytochemistry confirmed decreased AQP2 labeling in principal cells of both inner medullary and cortical collecting ducts. AQP2 labeling was predominantly associated with the apical plasma membrane and intracellular vesicles. Lithium treatment for 24 d caused a more extensive reduction of AQP2 levels, to 4+/-1% of control levels in the inner medulla and 4+/-2% in cortex, in association with severe polyuria. The similar degree of downregulation in medulla and cortex suggests that interstitial tonicity is not the major factor in the regulation of AQP2 expression. Consistent with this furosemide treatment did not alter AQP2 levels. In summary,hypokalemia, like lithium treatment, results in a decrease in AQP2 expression in rat collecting ducts, in parallel with the development of polyuria, and the degree of downregulation is consistent with the level of polyuria induced, supporting the view that there is a causative link.
AuthorsD Marples, J Frøkiaer, J Dørup, M A Knepper, S Nielsen
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 97 Issue 8 Pg. 1960-8 (Apr 15 1996) ISSN: 0021-9738 [Print] United States
PMID8621781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Aqp2 protein, rat
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins
  • Ion Channels
Topics
  • Animals
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins
  • Cell Membrane (metabolism, pathology, ultrastructure)
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Regulation
  • Hypokalemia (metabolism, pathology)
  • Immunoblotting
  • Ion Channels (analysis, biosynthesis)
  • Kidney Cortex (metabolism, pathology, ultrastructure)
  • Kidney Medulla (metabolism, pathology, ultrastructure)
  • Male
  • Microscopy, Electron
  • Polyuria
  • Potassium Deficiency (metabolism, urine)
  • Rats
  • Rats, Wistar
  • Thirst

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: