Effects of central sodium on epithelial sodium channels in rat brain

We evaluated the effects of intracerebroventricular (icv) infusion of [Na.sup.+]-rich artificial cerebrospinal fluid (aCSF), with or without the mineralocorticoid receptor (MR) blocker spironolactone, on epithelial [Na.sup.+] channel (ENaC) subunits and regulators, such as MR, serum/glucocorticoid-inducible kinase 1, neural precursor cells expressed developmentally downregulated 4-like gene, 11[beta]-hydroxylase, and aldosterone synthase, in brain regions of Wistar rats. The effects of icv infusion of the amiloride analog benzamil on brain tissue and CSF [Na.sup.+] concentration ([[Na.sup.+]]) were also assessed. In the choroid plexus and ependyma of the anteroventral third ventricle, ENaC subunits are present in apical and basal membranes. [Na.sup.+]-rich aCSF increased [beta]-ENaC mRNA and immunoreactivity in the choroid plexus and increased [alpha]- and [beta]-ENaC immunoreactivities in the ependyma. [Na.sup.+]-rich aCSF increased [alpha]- and [beta]-ENaC-gold-labeled particles in the microvilli of the choroid plexus and in basolateral membranes of the ependyma. Spironolactone only prevented the increase in [beta]-ENaC immunoreactivity in the choroid plexus and ependyma. In the supraoptic nucleus, paraventricular nucleus, and subfornical organ, [Na.sup.+]-rich aCSF did not affect mRNA expression levels of the studied genes. Benzamil significantly increased CSF [[Na.sup.+]] in the control, but not [Na.sup.+]-rich, aCSF group. In contrast, benzamil prevented the increase in hypothalamic tissue [[Na.sup.+]] by [Na.sup.+]-rich aCSF. These results suggest that CSF [Na.sup.+] upregulates ENaC expression in the brain epithelia, but not in the neurons of hypothalamic nuclei. ENaC in the choroid plexus and ependyma appear to contribute to regulation of [Na.sup.+] homeostasis in the brain. sodium-rich artificial cerebrospinal fluid; benzamil; cerebrospinal fluid sodium concentration doi: 10.1152/ajpregu.00834.2009.