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: 287/5/F932    most recent 00131.2004v2 00131.2004v1 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 (18) Citing Articles via Google Scholar Google Scholar Articles by Niisato, N. Articles by Marunaka, Y. Search for Related Content PubMed PubMed Citation Articles by Niisato, N. Articles by Marunaka, Y.

Involvement of cytosolic Cl^– in osmoregulation of -ENaC gene expression

Departments of ¹Molecular Cell Physiology and ³Respiratory Molecular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; and ²Center for Cell and Molecular Signaling and Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

Submitted 12 April 2004 ; accepted in final form 23 June 2004

Hypotonicity stimulates transepithelial Na⁺ reabsorption in renal A6 cells, but the mechanism for this stimulation is not fully understood. In the present study, we found that hypotonicity stimulated Na⁺ reabsorption through increases in mRNA expression of the -subunit of the epithelial Na⁺ channel (-ENaC). Hypotonicity decreases cytosolic Cl^– concentration; therefore, we hypothesized that hypotonicity-induced decreases in cytosolic Cl^– concentration could act as a signal to regulate Na⁺ reabsorption through changes in -ENaC mRNA expression. Treatment with the flavone apigenin, which activates the Na⁺-K⁺-2Cl^– cotransporter and increases cytosolic Cl^– concentration, markedly suppressed the hypotonicity-induced increase in -ENaC mRNA expression. On the other hand, blockade of the Na⁺-K⁺-2Cl^– cotransporter decreases cytosolic Cl^– concentration and increased -ENaC mRNA expression and Na⁺ reabsorption. Blocking Cl^– channels with 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) inhibited the hypotonicity-induced decrease in cytosolic Cl^– concentration and suppressed the hypotonicity-induced increase in -ENaC mRNA expression. Coapplication of NPPB and apigenin synergistically suppressed -ENaC mRNA expression. Thus, in every case, changes in cytosolic Cl^– concentration were associated with changes in -ENaC mRNA expression and changes in Na⁺ reabsorption: decreases in cytosolic Cl^– concentration increased -ENaC mRNA and increased Na⁺ reabsorption, whereas increases in cytosolic Cl^– concentration decreased -ENaC mRNA and decreased Na⁺ reabsorption. These findings support the hypothesis that changes in cytosolic Cl^– concentration are an important and novel signal in hypotonicity-induced regulation of -ENaC expression and Na⁺ reabsorption.

epithelial sodium channel; sodium transport; epithelial sodium channel regulation; hypotonicity; sodium-potassium-2 chloride cotransporter; chloride channels

This article has been cited by other articles:

				A. Taruno, N. Niisato, and Y. Marunaka Intracellular calcium plays a role as the second messenger of hypotonic stress in gene regulation of SGK1 and ENaC in renal epithelial A6 cells Am J Physiol Renal Physiol, January 1, 2008; 294(1): F177 - F186. [Abstract] [Full Text] [PDF]

				R. F. Husted, K. A. Volk, R. D. Sigmund, and J. B. Stokes Discordant effects of corticosteroids and expression of subunits on ENaC activity Am J Physiol Renal Physiol, September 1, 2007; 293(3): F813 - F820. [Abstract] [Full Text] [PDF]

				A. Taruno, N. Niisato, and Y. Marunaka Hypotonicity stimulates renal epithelial sodium transport by activating JNK via receptor tyrosine kinases Am J Physiol Renal Physiol, July 1, 2007; 293(1): F128 - F138. [Abstract] [Full Text] [PDF]

				H. Miyazaki, A. Shiozaki, N. Niisato, and Y. Marunaka Physiological significance of hypotonicity-induced regulatory volume decrease: reduction in intracellular Cl- concentration acting as an intracellular signaling Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1411 - F1417. [Abstract] [Full Text] [PDF]

				C. Leroy, A. Prive, J.-C. Bourret, Y. Berthiaume, P. Ferraro, and E. Brochiero Regulation of ENaC and CFTR expression with K+ channel modulators and effect on fluid absorption across alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1207 - L1219. [Abstract] [Full Text] [PDF]

				T. Bachhuber, J. Konig, T. Voelcker, B. Murle, R. Schreiber, and K. Kunzelmann Cl- Interference with the Epithelial Na+ Channel ENaC J. Biol. Chem., September 9, 2005; 280(36): 31587 - 31594. [Abstract] [Full Text] [PDF]

				R. G. Morris, S. Uchida, H. Brooks, M. A. Knepper, and C.-L. Chou Altered expression profile of transporters in the inner medullary collecting duct of aquaporin-1 knockout mice Am J Physiol Renal Physiol, July 1, 2005; 289(1): F194 - F199. [Abstract] [Full Text] [PDF]