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

Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York

Submitted 23 October 2005 ; accepted in final form 7 March 2006

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 -subunit, with apparent masses of 85 and 30 kDa, increased. Salt restriction also increased the abundance of the -subunit and produced an endoglycosidase H (Endo H)-resistant pool of this subunit. The abundance of the 90-kDa form of the -subunit decreased, whereas that of a 70-kDa form increased and this peptide also exhibited Endo H-resistant glycosylation. These changes in - and -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 - and - but not -subunits when animals were treated with exogenous aldosterone, and in - and - but not -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.

Na channels; Na depletion; Na repletion; aldosterone; potassium intake; proteolytic cleavage

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