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

Aldosterone controls sodium reabsorption and potassium secretion in the ald osterone-sensitive distal nephron (ASDN). Although clearance measurements h ave shown that aldosterone induces these transports within 30-60 min, no ea rly effects have been demonstrated in vivo at the level of the apical epith elial sodium channel (ENaC), the main effector of this regulation. Here we show by real-time RT-PCR and immunofluorescence that an aldosterone injecti on in adrenalectomized rats induces alpha -ENaC subunit expression along th e entire ASDN within 2 h, whereas beta- and gamma -ENaC are constitutively expressed. In the proximal ASDN portions only, ENaC is shifted toward the a pical cellular pole and the apical plasma membrane within 2 and 4 h, respec tively. To address the question of whether the early aldosterone-induced se rum and glucocorticoid-regulated kinase (SGK) might mediate this apical shi ft 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 act ivation and surface expression by a kinase activity-dependent mechanism. In conclusion, the rapid in vivo accumulation of SGK and alpha -ENaC after al dosterone injection takes place along the entire ASDN, whereas the transloc ation of alpha, beta, gamma -ENaC to the apical plasma membrane is restrict ed to its proximal portions. Results from oocyte experiments suggest the hy pothesis that a localized activation of SGK may play a role in the mediatio n of ENaC translocation.