Short-term aldosterone action on Na,K-ATPase surface expression: role of aldosterone-induced SGK1?
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 alpha subunit), whereas short-term effects appear to be mediated by the upregulation of short-lived elements of the machinery (e.g., ENaC alpha 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 mpkCCD(cl4), we showed that the parallel increase in Na,K-ATPase function [assessed by Na(+) pump current (I(p)) 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 alpha1 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.
Verrey
François
F
Institute of Physiology, University of Zurich, Switzerland. verrey@access.unizh.ch
Summa
Vanessa
V
Heitzmann
Dirk
D
Mordasini
David
D
Vandewalle
Alain
A
Féraille
Eric
E
Zecevic
Marija
M
D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D053503:Epithelial Sodium Channels; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins; D007668:Kidney / Q000201:enzymology; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015222:Sodium Channels / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D015222:Sodium Channels; D000254:Sodium-Potassium-Exchanging ATPase; D000099184:Serum-Glucocorticoid Regulated Kinases