HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/F1127    most recent 00387.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Pondugula, S. R. Articles by Marcus, D. C. Search for Related Content PubMed PubMed Citation Articles by Pondugula, S. R. Articles by Marcus, D. C.

Glucocorticoids stimulate cation absorption by semicircular canal duct epithelium via epithelial sodium channel

Cellular Biophysics Laboratory, Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506

Submitted 3 November 2003 ; accepted in final form 3 February 2004

The semicircular canal duct (SCCD) epithelium is a vestibular epithelial domain that was recently shown to actively contribute to endolymph homeostasis by Cl^– secretion under control of ₂-adrenergic stimulation. By analogy to other Cl^– secretory epithelia, we hypothesized that SCCD also provides an active absorptive pathway for Na⁺ under corticosteroid control. Measurements of short-circuit current (I_sc) demonstrated stimulation (7–24 h) by the glucocorticoids hydrocortisone (EC₅₀ 13 nM), corticosterone (33 nM), prednisolone (70 nM), and dexamethasone (13 nM) over physiologically and therapeutically relevant concentrations and its block by amiloride (IC₅₀ 470 nM) and benzamil (57 nM), inhibitors of the epithelial sodium channel (ENaC). I_sc was also partially inhibited by basolateral ouabain and Ba²⁺, indicating the participation of Na⁺-K⁺-ATPase and a K⁺ channel in Na⁺ transport. By contrast, aldosterone stimulated I_sc only at unphysiologically high concentrations (EC₅₀ 102 nM). The action of all steroids was blocked by mifepristone (RU-486; K_d 0.3 nM) but not by spironolactone (K_d 0.7 µM). Expression of mRNA for the -, -, and -subunits of ENaC was demonstrated in the presence and absence of glucocorticoids. These findings are the first to identify SCCD in the vestibular labyrinth as a site of physiologically significant ENaC-mediated Na⁺ absorption and osmotically coupled water flux. They further demonstrate regulation of Na⁺ transport by natural and therapeutic glucocorticoids. The results provide for the first time an understanding of the therapeutic benefit of glucocorticoids in the treatment of Meniere's disease, a condition that is associated with increased luminal fluid volume.

rat; inner ear; vestibular labyrinth; dexamethasone; prednisolone; cortisol (hydrocortisone)

This article has been cited by other articles:

				F. Lang, V. Vallon, M. Knipper, and P. Wangemann Functional significance of channels and transporters expressed in the inner ear and kidney Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1187 - C1208. [Abstract] [Full Text] [PDF]

				S. R. Pondugula, N. N. Raveendran, Z. Ergonul, Y. Deng, J. Chen, J. D. Sanneman, L. G. Palmer, and D. C. Marcus Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat Physiol Genomics, January 12, 2006; 24(2): 114 - 123. [Abstract] [Full Text] [PDF]