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: 24/2/114    most recent 00006.2005v1 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 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 Web of Science (4) 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.

Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat

¹ Cellular Biophysics Laboratory, Department of Anatomy and Physiology
² Division of Biology, Bioinformatics Center, Kansas State University, Manhattan, Kansas
³ Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York

The lumen of the inner ear has an unusually low concentration of endolymphatic Na⁺, which is important for transduction processes. We have recently shown that glucocorticoid receptors (GR) stimulate absorption of Na⁺ by semicircular canal duct (SCCD) epithelia. In the present study, we sought to determine the presence of genes involved in the control of the amiloride-sensitive Na⁺ transport pathway in rat SCCD epithelia and whether their level of expression was regulated by glucocorticoids using quantitative real-time RT-PCR. Transcripts were present for -, ß-, and -subunits of the epithelial sodium channel (ENaC); the ₁-, ₃-, ß₁-, and ß₃-isoforms of Na⁺-K⁺-ATPase; inwardly rectifying potassium channels [IC₅₀ of short circuit current (I_sc) for Ba²⁺: 210 µM] Kir2.1, Kir2.2, Kir2.3, Kir2.4, Kir3.1, Kir3.3, Kir4.1, Kir4.2, Kir5.1, and Kir7.1; sulfonyl urea receptor 1 (SUR1); GR; mineralocorticoid receptor (MR); 11ß-hydroxysteroid dehydrogenase (11ß-HSD) types 1 and 2; serum- and glucocorticoid-regulated kinase 1 (Sgk1); and neural precursor cell-expressed developmentally downregulated 4-2 (Nedd4-2). On the other hand, transcripts for the ₄-subunit of Na⁺-K⁺-ATPase, Kir1.1, Kir3.2, Kir3.4, Kir6.1, Kir6.2, and SUR2 were found to be absent, and I_sc was not inhibited by glibenclamide. Dexamethasone (100 nM for 24 h) not only upregulated the transcript expression of -ENaC (4-fold), ß₂-subunit (2-fold) and ß₃-subunit (8-fold) of Na⁺-K⁺-ATPase, Kir2.1 (5-fold), Kir2.2 (9-fold), Kir2.4 (3-fold), Kir3.1 ( 3- fold), Kir3.3 (2-fold), Kir4.2 (3-fold ), Kir7.1 (2-fold), Sgk1 (4-fold), and Nedd4-2 (2-fold) but also downregulated GR (3-fold) and 11ß-HSD1 (2-fold). Expression of GR and 11ß-HSD1 was higher than MR and 11ß-HSD2 in the absence of dexamethasone. Dexamethasone altered transcript expression levels (-ENaC and Sgk1) by activation of GR but not MR. Proteins were present for the -, ß-, and -subunits of ENaC and Sgk1, and expression of - and -ENaC was upregulated by dexamethasone. These findings are consistent with the genomic stimulation by glucocorticoids of Na⁺ absorption by SCCD and provide an understanding of the therapeutic action of glucocorticoids in the treatment of Meniere's disease.

inner ear; vestibular labyrinth; dexamethasone

This article has been cited by other articles:

				S. H. Kim, K. X. Kim, N. N. Raveendran, T. Wu, S. R. Pondugula, and D. C. Marcus Regulation of ENaC-mediated sodium transport by glucocorticoids in Reissner's membrane epithelium Am J Physiol Cell Physiol, March 1, 2009; 296(3): C544 - C557. [Abstract] [Full Text] [PDF]

				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. M. Clancy, S. B. Boyer, and P. A. Slesinger Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels J. Neurosci., June 13, 2007; 27(24): 6388 - 6399. [Abstract] [Full Text] [PDF]