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

Am J Physiol Renal Physiol. 2001 Apr;280(4):F675-82. doi: 10.1152/ajprenal.2001.280.4.F675.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / pharmacology*
  • Animals
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Cell Membrane / metabolism
  • Cell Polarity / physiology
  • Epithelial Sodium Channels
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Immediate-Early Proteins
  • In Vitro Techniques
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / enzymology*
  • Male
  • Nuclear Proteins*
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Sodium / metabolism
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Xenopus laevis

Substances

  • Epithelial Sodium Channels
  • Immediate-Early Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Sodium Channels
  • Aldosterone
  • Sodium
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase