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: 287/2/L411    most recent 00407.2003v1 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 (14) Citing Articles via Google Scholar Google Scholar Articles by Ramminger, S. J. Articles by Wilson, S. M. Search for Related Content PubMed PubMed Citation Articles by Ramminger, S. J. Articles by Wilson, S. M.

A regulated apical Na⁺ conductance in dexamethasone-treated H441 airway epithelial cells

Lung Membrane Transport Group, Division of Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom

Submitted 25 November 2003 ; accepted in final form 10 April 2004

Treating H441 cells with dexamethasone raised the abundance of mRNA encoding the epithelial Na⁺ channel - and -subunits and increased transepithelial ion transport (measured as short-circuit current, I_sc) from <4 µA·cm^–2 to 10–20 µA·cm^–2. This dexamethasone-stimulated ion transport was blocked by amiloride analogs with a rank order of potency of benzamil amiloride > EIPA and can thus be attributed to active Na⁺ absorption. Studies of apically permeabilized cells showed that this increased transport activity did not reflect a rise in Na⁺ pump capacity, whereas studies of basolateral permeabilized cells demonstrated that dexamethasone increased apical Na⁺ conductance (G_Na) from a negligible value to 100–200 µS·cm^–2. Experiments that explored the ionic selectivity of this dexamethasone-induced conductance showed that it was equally permeable to Na⁺ and Li⁺ and that the permeability to these cations was approximately fourfold greater than to K⁺. There was also a small permeability to N-methyl-D-glucammonium, a nominally impermeant cation. Forskolin, an agent that increases cellular cAMP content, caused an 60% increase in I_sc, and measurements made after these cells had been basolaterally permeabilized demonstrated that this response was associated with a rise in G_Na. This cAMP-dependent control over G_Na was disrupted by brefeldin A, an inhibitor of vesicular trafficking. Dexamethasone thus stimulates Na⁺ transport in H441 cells by evoking expression of an amiloride-sensitive apical conductance that displays moderate ionic selectivity and is subject to acute control via a cAMP-dependent pathway.

airway epithelium; epithelial sodium channel; Ussing chambers; glucocorticoids; apical membrane

This article has been cited by other articles:

				O. J. Mace, A. M. Woollhead, and D. L. Baines AICAR activates AMPK and alters PIP2 association with the epithelial sodium channel ENaC to inhibit Na+ transport in H441 lung epithelial cells J. Physiol., September 15, 2008; 586(18): 4541 - 4557. [Abstract] [Full Text] [PDF]

				S. G. Brown, M. Gallacher, R. E. Olver, and S. M. Wilson The regulation of selective and nonselective Na+ conductances in H441 human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L942 - L954. [Abstract] [Full Text] [PDF]

				R. R. Quesnell, X. Han, and B. D. Schultz Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1739 - C1745. [Abstract] [Full Text] [PDF]

				S. K. Inglis, S. G. Brown, M. J. Constable, N. McTavish, R. E. Olver, and S. M. Wilson A Ba2+-resistant, acid-sensitive K+ conductance in Na+-absorbing H441 human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1304 - L1312. [Abstract] [Full Text] [PDF]

				S. M. Wilson, S. G. Brown, N. McTavish, R. P. McNeill, E. M. Husband, S. K. Inglis, R. E. Olver, and M. T. Clunes Expression of intermediate-conductance, Ca2+-activated K+ channel (KCNN4) in H441 human distal airway epithelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L957 - L965. [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]

				A. M Woollhead, J. W Scott, D. G. Hardie, and D. L Baines Phenformin and 5-aminoimidazole-4-carboxamide-1-{beta}-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells J. Physiol., August 1, 2005; 566(3): 781 - 792. [Abstract] [Full Text] [PDF]