Effects of Central Sodium On Epithelial Sodium Channels (ENaC) Expression In Rat Brain

Abstract

Mineralocorticoid receptors (MR) and ENaC mediate pressor responses to increases of CSF [Na+]. We evaluated MR‐dependent effects of central sodium on ENaC subunits (α, β ,γ) expression as well as its endogenous regulator, Sgk1. Male Wistar rats were infused icv for 2 weeks with regular or Na+‐rich artificial CSF (aCSF) with or without spironolactone. Brain areas studied included ependyma of the anteroventral third ventricle, supraoptic nucleus (SON), paraventricular nucleus (PVN) and subfornical organ (SFO). In ependyma, Na+‐rich aCSF increased expression of the α and β subunits, primarily in the basolateral membrane. Spironolactone did not prevent these changes. In SON, Na+ increased expression of mRNA for α and γ subunits without affecting α protein levels, and increased Sgk1 mRNA levels although a decrease in phosphorylated Sgk1 protein (p‐Sgk1) was noted. Spironolactone prevented the increases in mRNA encoding ENaC but not Sgk1. In PVN, Na+ decreased the α mRNA but not protein levels, and significantly decreased p‐Sgk1 protein with no change in Sgk1 mRNA. In SFO, Na+ only significantly increased γ mRNA. Spironolactone did not prevent the changes in ENaC mRNA in PVN or SFO. Regulation of ENaC and Sgk1 expression in the brain in response to Na+ appears quite region specific. Spironolactone prevents only some of the increases in ENaC subunit expression implying that, in addition to aldosterone, other regulators are involved.