Estradiol increases plasma membrane insertion of αENaC in the lung

Abstract

Sodium reabsorption through alveolar epithelial sodium channels (ENaC) is the major driving force for lung fluid clearance. Recent evidence shows greater rates of lung fluid clearance in females than males suggesting that female sex hormones might regulate ENaC function. Using cell‐attached patch clamp, we have previously shown that β‐estradiol (E2) activates both highly‐selective and non‐selective ENaC in rat alveolar cells (L2). To extend that study, we examined possible mechanisms by which E2 increases ENaC activity. We first investigated whether E2 (200 pg/mL) altered αENaC gene expression in alveolar (L2) cells. E2 did not affect mRNA or protein levels of αENaC. Using cell surface biotinylation, we also examined differences in apical plasma membrane abundance of αENaC in vehicle and E2‐treated cells. There was ~3 fold increase in αENaC (60kDa) abundance with E2 treatment. Finally, we examined plasma membrane abundance of αENaC in lungs from female rats at the diestrus, proestrus, and estrus phases of the estrous cycle. Consistent with an effect of E2, we observed ~3 fold greater abundance of αENaC (60–75kDa) in lungs from proestrus rats. These results suggest that greater insertion of αENaC into the plasma membrane is one mechanism by which E2 increases alveolar ENaC activity. Future studies will focus on which estrogen receptor mediates this effect.Funding: NIH R37DK037963, K12GM000680 and T32HL076118