Basolateral chloride current in human airway epithelia

• Published in: American journal of physiology. Lung cellular and molecular physiology 2007-10, Vol.293 (4), p.L991-L999
• Main Authors: Itani, Omar A, Lamb, Fred S, Melvin, James E, Welsh, Michael J
• Format: Article
• Language: English
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology; Adenosine triphosphatase; Airway management; Animals; Bronchi - cytology; Bronchi - metabolism; Cells; Cells, Cultured; Chemical compounds; Chloride Channels - antagonists & inhibitors; Chloride Channels - deficiency; Chloride Channels - physiology; Cyclic AMP - metabolism; Cystic fibrosis; Cystic Fibrosis - metabolism; Electric Conductivity; Enzyme Activation - physiology; Epithelial Cells - metabolism; Humans; Hydrogen-Ion Concentration; Ion Transport - drug effects; Mice; Mice, Knockout; Protein Kinase C - metabolism; Signal Transduction - physiology; Sorption; Studies; Trachea - cytology; Trachea - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00077.2007

1 Howard Hughes Medical Institute, Departments of 2 Internal Medicine, 3 Pediatrics, and 4 Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; and 5 Center 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 Ca 2+ 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 Address for reprint requests and other correspondence: M. J. Welsh, 500 EMRB, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Univ. of Iowa, Iowa City, IA 52242 (e-mail: michael-welsh{at}uiowa.edu )