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 to 60 min, so far 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 (ADX) rats induces ENaC a subunit expression along the entire ASDN within 2 h, whereas the remaining two subunits, b and g , 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 whether the early aldosterone-induced serum and glucocorticoid-regulated kinase (SGK) might mediate this apical shift of ENaC, we analyzed SGK induction in vivo. 2 h after aldosterone, SGK was highly induced in all segment-specific cells of the ASDN and its level decreased thereafter. In Xenopus oocytes, SGK induced ENaC activation and surface expression by a kinase activity-dependent mechanism. In conclusion, the rapid in vivo accumulation of SGK and a ENaC after aldosterone injection, takes place along the entire ASDN, whereas the translocation of a ,b ,g 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.

#The first two authors contributed equally to this work