Aldosterone induces rapid apical translocation of ENaC in early portion of renal collecting system: possible role of SGK.
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.
Institute of Anatomy, University of Zürich, CH-8057 Zürich, Switzerland.
J
J
Loffing
M
M
Zecevic
E
E
Féraille
B
B
Kaissling
C
C
Asher
B C
BC
Rossier
G L
GL
Firestone
D
D
Pearce
F
F
Verrey
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology; D053503:Epithelial Sodium Channels; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017874:Immediate-Early Proteins; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009687:Nuclear Proteins; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; 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; D012964:Sodium; D015222:Sodium Channels; D000099184:Serum-Glucocorticoid Regulated Kinases