ALDOSTERONE-MEDIATED NA K-ATPASE EXPRESSION IS ALPHA-1 ISOFORM-SPECIFIC IN THE RENAL CORTICAL COLLECTING DUCT/

Citation
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
Citations number
59
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
268
Issue
31
Year of publication
1993
Pages
23469 - 23476
Database
ISI
SICI code
0021-9258(1993)268:31<23469:ANKEIA>2.0.ZU;2-G
Abstract
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.