Regulation of maturation and processing of ENaC subunits in the rat kidney

Antibodies directed against subunits of the epithelial Na channel ( ENaC) were used together with electrophysiological measurements in the cortical collecting duct to investigate the processing of the proteins in rat kidney with changes in Na or K intake. When animals were maintained on a low-Na diet for 7-9 days, the abundance of two forms of the alpha-subunit, with apparent masses of 85 and 30 kDa, increased. Salt restriction also increased the abundance of the beta-subunit and produced an endoglycosidase H ( Endo H)-resistant pool of this subunit. The abundance of the 90-kDa form of the alpha-subunit decreased, whereas that of a 70-kDa form increased and this peptide also exhibited Endo H-resistant glycosylation. These changes in alpha- and gamma-subunits were correlated with increases in Na conductance elicited by a 4-h infusion with aldosterone. Changes in all three subunits were correlated with decreases in Na conductance when Na-deprived animals drank saline for 5 h. We conclude that ENaC subunits are mainly in an immature form in salt-replete rats. With Na depletion, the subunits mature in a process that involves proteolytic cleavage and further glycosylation. Similar changes occurred in alpha- and gamma- but not beta-subunits when animals were treated with exogenous aldosterone, and in alpha- and gamma- but not beta-subunits when animals were fed a high-K diet. Changes in the processing and maturation of the channels occur rapidly enough to be involved in the daily regulation of ENaC activity and Na reabsorption by the kidney.