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Am J Physiol Renal Physiol 280: F675-F682, 2001;
0363-6127/01 $5.00
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Vol. 280, Issue 4, F675-F682, April 2001

Aldosterone induces rapid apical translocation of ENaC in early portion of renal collecting system: possible role of SGK

Johannes Loffing2,*, Marija Zecevic1,*, Eric Féraille3, Brigitte Kaissling2, Carol Asher4, Bernard C. Rossier5, Gary L. Firestone6, David Pearce7, and François Verrey1

1 Institute of Physiology and 2 Institute of Anatomy, University of Zürich, CH-8057 Zürich; 3 Division de Néphrologie, Hôpital Cantonal Universitaire, CH-1211 Geneva; 4 Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel; 5 Institut de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland; 6 Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of Califonia, Berkeley 94720; and 7 Division of Nephrology, Department of Medicine and Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California 94143

Aldosterone controls sodium reabsorption and potassium secretion in the aldosterone-sensitive distal nephron (ASDN). Although clearance measurements have shown that aldosterone induces these transports within 30-60 min, no early effects have been demonstrated in vivo at the level of the apical epithelial sodium channel (ENaC), the main effector of this regulation. Here we show by real-time RT-PCR and immunofluorescence that an aldosterone injection in adrenalectomized rats induces alpha -ENaC subunit expression along the entire ASDN within 2 h, whereas beta - and gamma -ENaC are constitutively expressed. In the proximal ASDN portions only, ENaC is shifted toward the apical cellular pole and the apical plasma membrane within 2 and 4 h, respectively. To address the question of whether the early aldosterone-induced serum and glucocorticoid-regulated kinase (SGK) might mediate this apical shift of ENaC, we analyzed SGK induction in vivo. Two hours after aldosterone, SGK was highly induced in all segment-specific cells of the ASDN, and its level decreased thereafter. In Xenopus laevis oocytes, SGK induced ENaC activation and surface expression by a kinase activity-dependent mechanism. In conclusion, the rapid in vivo accumulation of SGK and alpha -ENaC after aldosterone injection takes place along the entire ASDN, whereas the translocation of alpha ,beta ,gamma -ENaC to the apical plasma membrane is restricted to its proximal portions. Results from oocyte experiments suggest the hypothesis that a localized activation of SGK may play a role in the mediation of ENaC translocation.

Xenopus laevis oocytes; sodium transport; kidney; collecting duct; epithelial sodium channel; serum and glucocorticoid-regulated kinase

* J. Loffing and M. Zecevic contributed equally to this work.




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