1. Segmental variability of ENaC subunit expression in rat colon during dietary sodium depletion.
- Author
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Greig, E. R., Baker, E. H., Mathialahan, T., Boot-Handford, R. P., and Sandle, G. I.
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COLON (Anatomy) ,SODIUM channels ,ALDOSTERONE ,MESSENGER RNA ,PROTEINS ,HYPERALDOSTERONISM - Abstract
In rat distal colon, aldosterone has little effect on Na
+ channel (ENaC) α-subunit levels but increases the expression of the β- and γ-subunits and stimulates electrogenic Na+ transport. By contrast, the molecular basis of aldosterone's inability to stimulate electrogenic Na+ transport in the proximal colon is unclear. We therefore compared the effects of hyperaldosteronism secondary to 10 days dietary Na+ depletion on ENaC subunit expression in rat proximal and distal colon. Northern analyses revealed appreciable and similar levels of α-subunit mRNA throughout the colon in control and Na+ -depleted animals. By contrast, Na+ depletion substantially enhanced β-subunit mRNA expression in the distal colon, but had no effect on the low expression levels of β-subunit mRNA in the proximal colon. Expression of the γ-subunit, evaluated by PCR, was also restricted to the distal colon of Na+ -depleted animals. Western analyses demonstrated similar levels of α-subunit protein in the proximal and distal colon of both groups of animals, whereas β-subunit and γ-subunit proteins were detected solely or predominantly in the distal colon of the Na+ -depleted animals. Immunocytochemistry confirmed that significant levels of all three subunit proteins only occurred in the apical membrane of surface cells in the distal colon of Na+ -depleted animals. Our findings are consistent with previous studies demonstrating that aldosterone stimulates electrogenic Na+ transport in rat distal colon by increasing the expression of β- and γ-subunit mRNA and protein, and thus the amount of functional heteromeric ENaC protein in the apical domain. They also show that aldosterone is incapable of stimulating electrogenic Na+ transport in rat proximal colon (despite the presence of α-subunit mRNA and protein) because of its inability to enhance β- and γ-subunit expression in this segment. [ABSTRACT FROM AUTHOR]- Published
- 2002
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