Cystic Fibrosis

New cell biology research reported from University of Iowa, Howard Hughes Medical Institute

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"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," wrote O.A. Itani and colleagues, University of Iowa, Howard Hughes Medical Institute.

The researchers concluded: "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."

Itani and colleagues published their study in American Journal of Physiology - Lung Cellular and Molecular Physiology (Basolateral chloride current in human airway epithelia. American Journal of Physiology - Lung Cellular and Molecular Physiology, 2007;293(4):L991-9).

For additional information, contact O.A. Itani, University of Iowa, Howard Hughes Medical Institute, Iowa City, IA 52242 USA..

Publisher contact information for the American Journal of Physiology - Lung Cellular and Molecular Physiology is: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA.

Keywords: United States, Iowa City, Cell Biology, Cellular, Cystic Fibrosis, Genetics, Physiology, Pulmonology.

This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.