Regulation of ENaC‐mediated sodium transport by glucocorticoids in Reissner's membrane epithelium

Abstract

Reissner's membrane (RM) epithelium forms much of the barrier that sustains the large ionic differences between cochlear endolymph and perilymph. We reported that RM contributes to normal cochlear function by absorption of Na from endolymph via the epithelial sodium channel (ENaC) in gerbil inner ear [Lee et al, Neuroscience, 2003].In the present study, we sought in mouse RM 1) to determine the presence of genes involved in the Na transport pathway, 2) to determine whether their level of expression was regulated by corticosteroids using gene array and quantitative RT‐PCR and 3) to obtain functional evidence for these genes by electrophysiologic and pharmacologic means. Transcripts were present for the α‐, β‐, γ‐subunits of ENaC; the steroid receptors GR (glucocorticoid receptor) and MR (mineralocorticoid receptor); the GR agonist‐regulator 11β‐HSD1; Na transport control components Sgk1 and Nedd4‐2. Expression of the MR agonist‐regulator 11β‐HSD2 was near the lower limit of detection. Dexamethasone upregulated transcript expression of α‐ and β‐subunits of ENaC (∼6 and ∼3 fold). Currents directed into the endolymphatic face of RM were sensitive to amiloride and benzamil, but not EIPA. The currents were also inhibited by ouabain and K‐channel blockers (TEA and clotrimazole). These molecular and functional observations are consistent with Na absorption by RM in the mouse that is mediated by apical ENaC, basolateral Na‐pump and K channels, and that is under the control of glucocorticoids but not mineralocorticoids. These results provide an understanding and molecular definition of one possible mode of therapeutic action of glucocorticoids in the treatment of Meniere's disease.Supported by NIH grants R01‐DC00212, P20‐PR017686.