Pa. Welling et al., ALDOSTERONE-MEDIATED NA K-ATPASE EXPRESSION IS ALPHA-1 ISOFORM-SPECIFIC IN THE RENAL CORTICAL COLLECTING DUCT/, The Journal of biological chemistry, 268(31), 1993, pp. 23469-23476
In the renal cortical collecting duct (CCD), mineral-ocorticoid hormon
es, like aldosterone, augment the abundance of Na/K-ATPase molecules.
It has been postulated that this response involves an isoform switch o
f the Na/K-ATPase catalytic subunit, alpha, as the molecular basis for
the differential regulation of mineralocorticoid-induced and constitu
tively expressed Na/K-ATPase pools. In opposition to this attractive h
ypothesis, three lines of independent evidence are presented which dem
onstrate that the CCD exclusively expresses the alpha1 form despite mi
neralocorticoid-mediated changes in functional Na/K pump density. Firs
t, aldosterone increased [H-3]ouabain binding in CCD 2.5-fold without
changing the ouabain dissociation constant. Second, an electrophysiolo
gical assay for pump activity revealed that aldosterone increased maxi
mum Na/K pump current in parallel with the change in ouabain binding w
ithout altering the apparent sodium affinity. Third, Western blot anal
ysis with alpha isoform-specific, antipeptide antibodies demonstrated
that aldosterone exclusively increased the total chemical pool of the
alpha1 form of the pump without inducing other alpha subunit isoforms.
In summary, aldosterone increases the abundance of Na/K-ATPase molecu
les in the CCD which are pharmacologically, physiologically, and chemi
cally indistinguishable from those that are normally expressed.