HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 294/6/F1298    most recent 00579.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Fejes-Tóth, G. Articles by Palmer, L. G. Search for Related Content PubMed PubMed Citation Articles by Fejes-Tóth, G. Articles by Palmer, L. G.

EDITORIAL FOCUS

Epithelial Na⁺ channel activation and processing in mice lacking SGK1

¹Department of Physiology, Dartmouth School of Medicine, Lebanon, Hew Hampshire; and ²Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York

Submitted 4 December 2007 ; accepted in final form 26 March 2008

Amiloride-sensitive Na⁺ channel activity was examined in the cortical collecting ducts of a mouse line (SGK1^–/–) deficient in the serum- and glucocorticoid-dependent protein kinase SGK1. This activity was correlated with changes in renal Na handling and in the maturation of epithelial Na⁺ channel (ENaC) protein. Neither SGK1^–/– mice nor paired SGK1^+/+ animals expressed detectable channel activity, measured as amiloride-sensitive whole-cell current (I_Na), under control conditions with standard chow. Administration of aldosterone (0.5 µg/h via osmotic minipump for 7 days) increased I_Na to a similar extent in SGK1^+/+ (378 ± 61 pA/cell at –100 mV) and in SGK1^–/– (350 ± 57 pA/cell) animals. However, the maturation of ENaC, assessed as the ratio of cleaved to full-length forms of -ENaC, was more pronounced in SGK^+/+ mice. The SGK1^–/– animals exhibited a salt-wasting phenotype when kept on a low-Na diet for up to 2 days, losing significantly more Na in the urine than wild-type mice. Under these conditions, I_Na was enhanced more in SGK1^–/– (94 ± 14 pA/cell) than in SGK^+/+ (23 ± 5 pA/cell) genotypes. Despite the larger currents, the ratio of cleaved to full-length -ENaC was lower in the knockout animals. The mice also expressed a smaller amount of Na⁺-Cl^– cotransporter protein under Na-depleted conditions. These results indicated that SGK1 is essential for optimal processing of ENaC but is not required for activation of the channel by aldosterone.

epithelial sodium channel; proteolysis; sodium reabsorption; cortical collecting duct

This article has been cited by other articles:

				D. Ruffieux-Daidie, O. Poirot, S. Boulkroun, F. Verrey, S. Kellenberger, and O. Staub Deubiquitylation Regulates Activation and Proteolytic Cleavage of ENaC J. Am. Soc. Nephrol., November 1, 2008; 19(11): 2170 - 2180. [Abstract] [Full Text] [PDF]

				F. J. McDonald A new SGK1 knockout mouse Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1296 - F1297. [Full Text] [PDF]