Abstract
Aldosterone controls extracellular volume and blood pressure by regulating Na+ reabsorption, in particular by epithelia of the distal nephron. A main regulatory site of this transcellular transport is the epithelial sodium channel (ENaC) that mediates luminal Na+ influx. The Na,K-ATPase (Na+ pump) that coordinately extrudes Na+ across the basolateral membrane is known to be regulated by short term aldosterone as well. We now show that in the cortical collecting duct (CCD) from adrenalectomized rats, the increase in Na,K-ATPase activity (approximately 3-fold in 3 h), induced by a single aldosterone injection, can be fully accounted by the increase in Na,K-ATPase cell surface expression (+ 497 +/- 35%). The short term aldosterone action was further investigated in cultured mouse collecting duct principal cells mpkCCD(cl4). Within 2 h, maximal Na,K-ATPase function assessed by Na+ pump current (I(p)) measurements and Na,K-ATPase cell surface expression were increased by 20-50%. Aldosterone did not modify the Na+ dependence of the Na+ pumps and induced transcription- and translation-dependent actions on pump surface expression and current independently of ENaC-mediated Na+ influx. In summary, short term aldosterone directly increases the cell surface expression of pre-existing Na+ pumps in kidney CCD target cells. Thus, aldosterone controls Na+ reabsorption in the short term not only by regulating the apical cell surface expression of ENaC (Loffing, J., Zecevic, M., Feraille, E., Kaissling, B., Asher, C., Rossier, B. C., Firestone, G. L., Pearce, D., and Verrey, F. (2001) Am. J. Physiol. 280, F675-F682) but also by coordinately acting on the basolateral cell surface expression of the Na,K-ATPase.
Highlights
The mineralocorticoid hormone aldosterone plays a central role in the regulatory network that controls body sodium and volume homeostasis [1]
Short Term Aldosterone Increases in Vivo Na,K-ATPase Hydrolytic Activity and Cell Surface Expression in Intact Rat Cortical Collecting Duct—The effect of a single intravenous infusion of aldosterone on Na,K-ATPase activity and expression was investigated in collecting duct (CCD) of ADX rats
To test the hypothesis that it was mainly the cell surface pool of the Na,K-ATPase that was increased by the short aldosterone treatment, we performed cell surface biotinylation followed by precipitation with streptavidin-agarose beads and Western blotting
Summary
The mineralocorticoid hormone aldosterone plays a central role in the regulatory network that controls body sodium and volume homeostasis [1] It displays a potent Naϩ retaining action at the level of tight epithelia, in particular in the aldos-. The segment-specific cells of the ASDN express a transcellular pathway for Naϩ reabsorption that is composed of the luminal epithelial Naϩ channel (ENaC) and the basolateral Na,KATPase (Naϩ pump) The activity of this Naϩ reabsorptive pathway is controlled by aldosterone mostly via the mineralocorticoid receptor and to some extent via the glucocorticoid receptor [5,6,7,8]. As regards the mechanism by which ENaC is regulated, a recent study has shown that a single aldosterone injection given to adrenalectomized (ADX) rats induces the synthesis of new ENaC ␣-subunits and, in the early ASDN, the translocation of ␣, ,␥ENaC to the apical cell surface as well [4]
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