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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/L489    most recent 90282.2008v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Jeulin, C. Articles by Marano, F. Search for Related Content PubMed PubMed Citation Articles by Jeulin, C. Articles by Marano, F.

EGF mediates calcium-activated chloride channel activation in the human bronchial epithelial cell line 16HBE14o^–: involvement of tyrosine kinase p60^c-src

¹Laboratoire de Cytophysiologie et Toxicologie Cellulaire and ²Laboratoire de Physiopathologie de la Nutrition, Centre National de la Recherche Scientifique-ESA 7059, Université Paris 7 Denis Diderot, Paris, France

Submitted 18 April 2008 ; accepted in final form 26 June 2008

Particulate atmospheric pollutants interact with the human airway epithelium, which releases cytokines, chemokines, and EGF receptor (EGFR) ligands leading to proinflammatory responses. There is little information concerning the short-term effects of EGFR activation by extracellular ligands on ionic regulation of airway surface lining fluids. We identified in the membrane of human epithelial bronchial cells (16HBE14o^– line) an endogenous calcium- and voltage-dependent, outwardly rectifying small-conductance chloride channel (CACC), and we examined the effects of EGF on CACC activity. Ion channel currents were recorded with the patch-clamp technique. In cell-attached membrane patches, CACC were activated by exposure of the external surface of the cells to physiological concentrations of EGF without any change in cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and inhibited by tyrphostin AG-1478 (an inhibitor of EGFR that also blocks EGF-dependent Src family kinase activation). EGF activation of c-Src protein in 16HBE14o^– cells was observed, and the signaling pathway elicited by EGFR was blocked by tyrphostin AG-1478. In excised inside-out membrane patches CACC were activated by exposure of the cytoplasmic face of the channels to the human recombinant Src(p60^c-src) kinase with endogenous or exogenous ATP and inhibited by -protein phosphatase. Secretion of EGFR ligands by epithelial airway cells exposed to pollutants would then elicit a rapid and direct ionic response of CACC mediated by EGFR activation via a Src kinase family-dependent signaling pathway.

calcium-activated chloride channels; patch-clamp technique; epidermal growth factor receptor; Src tyrosine kinase