Aldosterone Mediated Regulation of Epithelial Sodium Channel (ENaC) Subunits in the Rat Hypothalamus
© 2018 IBRO Current evidence suggests that the epithelial Na + channel (ENaC) in the brain plays a significant role in the development of hypertension. ENaC is present in vasopressin (VP) neurons in the hypothalamus, suggesting that ENaC in VP neurons is involved in the regulation of blood pressure. Our recent study demonstrated that high dietary salt intake caused an increase in the expression and activity of ENaC that were responsible for the more depolarized basal membrane potential in VP neurons. A known regulator of ENaC expression, the mineralocorticoid receptor (MR), is present in VP neurons, suggesting that ENaC expression in VP neurons is regulated by aldosterone. In this study, the effects of aldosterone and corticosterone on ENaC were examined in acute hypothalamic slices. Real-time PCR and Western blot analysis showed that aldosterone and corticosterone treatment resulted in a significant increase in the expression of γENaC, but not α- or βENaC, and that this expression was attenuated by MR and glucocorticoid receptor (GR) antagonists. Moreover, chromatin immunoprecipitation demonstrated that the aldosterone-MR complex directly interacts with the promoter region of the γENaC gene. However, the treatment with aldosterone did not cause subcellular translocation of ENaC toward the plasma membrane nor an increase in ENaC Na + -leak current. These results indicate that expression of γENaC in VP neurons is induced by aldosterone and corticosterone through their MR and GR, respectively; however, aldosterone or corticosterone alone is not sufficient enough to increase ENaC current when they are applied to hypothalamic slices in vitro.
Publication Source (Journal or Book title)
Mills, N., Sharma, K., Haque, M., Moore, M., & Teruyama, R. (2018). Aldosterone Mediated Regulation of Epithelial Sodium Channel (ENaC) Subunits in the Rat Hypothalamus. Neuroscience, 390, 278-292. https://doi.org/10.1016/j.neuroscience.2018.08.031