Effects of central sodium on epithelial sodium channels in rat brain

Wang HW, Amin MS, El-Shahat E, Huang BS, Tuana BS, Leenen FH. Effects of central sodium on epithelial sodium channels in rat brain. Am J Physiol Regul Integr Comp Physiol 299: R222-R233, 2010. First published April 28, 2010; doi:10.1152/ajpregu.00834.2009.-We evaluated the effects of intracerebroventricular (icv) infusion of Na+-rich artificial cerebrospinal fluid (aCSF), with or without the mineralocorticoid receptor (MR) blocker spironolactone, on epithelial Na+ 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+ concentration ([Na+]) were also assessed. In the choroid plexus and ependyma of the anteroventral third ventricle, ENaC subunits are present in apical and basal membranes. Na+-rich aCSF increased beta-ENaC mRNA and immunoreactivity in the choroid plexus and increased alpha- and beta-ENaC immunoreactivities in the ependyma. Na+-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+-rich aCSF did not affect mRNA expression levels of the studied genes. Benzamil significantly increased CSF [Na+] in the control, but not Na+-rich, aCSF group. In contrast, benzamil prevented the increase in hypothalamic tissue [Na+] by Na+-rich aCSF. These results suggest that CSF Na+ 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+ homeostasis in the brain.