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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/L991    most recent 00077.2007v1 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 Google Scholar Google Scholar Articles by Itani, O. A. Articles by Welsh, M. J. Search for Related Content PubMed PubMed Citation Articles by Itani, O. A. Articles by Welsh, M. J.

Basolateral chloride current in human airway epithelia

¹Howard Hughes Medical Institute, Departments of ²Internal Medicine, ³Pediatrics, and ⁴Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and ⁵Center for Oral Biology, University of Rochester Medical Center, Rochester, New York

Submitted 27 February 2007 ; accepted in final form 20 July 2007

Electrolyte transport by airway epithelia regulates the quantity and composition of liquid covering the airways. Previous data indicate that airway epithelia can absorb NaCl. At the apical membrane, cystic fibrosis transmembrane conductance regulator (CFTR) provides a pathway for Cl^– absorption. However, the pathways for basolateral Cl^– exit are not well understood. Earlier studies, predominantly in cell lines, have reported that the basolateral membrane contains a Cl^– conductance. However, the properties have varied substantially in different epithelia. To better understand the basolateral Cl^– conductance in airway epithelia, we studied primary cultures of well-differentiated human airway epithelia. The basolateral membrane contained a Cl^– current that was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). The current-voltage relationship was nearly linear, and the halide selectivity was Cl^– > Br^– >> I^–. Several signaling pathways increased the current, including elevation of cellular levels of cAMP, activation of protein kinase C (PKC), and reduction of pH. In contrast, increasing cell Ca²⁺ and inducing cell swelling had no effect. The basolateral Cl^– current was present in both cystic fibrosis (CF) and non-CF airway epithelia. Likewise, airway epithelia from wild-type mice and mice with disrupted genes for ClC-2 or ClC-3 all showed similar Cl^– currents. These data suggest that the basolateral membrane of airway epithelia possesses a Cl^– conductance that is not due to CFTR, ClC-2, or ClC-3. Its regulation by cAMP and PKC signaling pathways suggests that coordinated regulation of Cl^– conductance in both apical and basolateral membranes may be important in controlling transepithelial Cl^– movement.

chloride channel; absorption; adenosine 3',5'-cyclic monophosphate; cystic fibrosis