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- Title
Short-Term Aldosterone Action on Na,K-ATPase Surface Expression.
- Authors
VERREY, FRANÇOIS; SUMMA, VANESSA; HEITZMANN, DIRK; MORDASINI, DAVID; VANDEWALLE, ALAIN; FERAILLE, ERIC; ZECEVIC, MARIJA
- Abstract
A bstract: Aldosterone controls extracellular volume and blood pressure by regulating Na+ reabsorption across epithelial cells of the aldosterone-sensitive distal nephron (ASDN). This effect is mediated by a coordinate action on the luminal channel ENaC (generally rate limiting) and the basolateral Na,K-ATPase. Long-term effects of aldosterone (starting within 3 to 6 hours and increasing over days) are mediated by the direct and indirect induction of stable elements of the Na+ transport machinery (e.g., Na,K-ATPase α subunit), whereas short-term effects appear to be mediated by the upregulation of short-lived elements of the machinery (e.g., ENaC α subunit) and of regulatory proteins, such as the serum- and glucocorticoid-regulated kinase SGK1. We have recently shown that in cortical collecting duct (CCD) from adrenalectomized (ADX) rats, the increase in Na,K-ATPase activity (approximately threefold in 3 h), induced by a single aldosterone injection, can be fully accounted for by the increase in Na,K-ATPase cell-surface expression. Using the model cell line mpkCCDcl4, we showed that the parallel increase in Na,K-ATPase function [assessed by Na+ pump current (Ip) measurements] and cell-surface expression depends on transcription and translation, and that it is not secondary to a change in apical Na+ influx. As a first approach to address the question whether the aldosterone-induced regulatory protein SGK1 might play a role in mediating Na,K-ATPase translocation, we have used the Xenopus laevis expression system. SGK1 coexpression indeed increased both the Na+ pump current and the surface expression of pumps containing the rat α1 subunits. In summary, aldosterone controls Na+ reabsorption in the short term not only by regulating the apical cell-surface expression of ENaC but also by coordinately acting on the basolateral cell-surface expression of the Na,K-ATPase. Results obtained in the Xenopus oocyte expression system suggest the possibility that this effect could be mediated in part by the aldosterone-induced kinase SGK1.
- Publication
Annals of the New York Academy of Sciences, 2003, Vol 986, Issue 1, p554
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.2003.tb07253.x