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J. Biol. Chem., Vol. 275, Issue 45, 35028-35033, November 10, 2000
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From the Calcium-activated Cl
Permeabilization via the P2X7 Purinoreceptor Reveals
the Presence of a Ca2+-activated Cl
Conductance in the Apical Membrane of Murine Tracheal Epithelial
Cells*
§,,,
Cystic Fibrosis/Pulmonary Research and
Clinical Treatment Center, University of North Carolina, Chapel
Hill, North Carolina 27599 and the ¶ School of Pharmacy and
Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, United
Kingdom
secretion is an important modulator of regulated ion transport in
murine airway epithelium and is mediated by an unidentified
Ca2+-stimulated Cl channel. We have
transfected immortalized murine tracheal epithelial cells with the
cDNA encoding the permeabilizing P2X7 purinoreceptor (P2X7-R) to selectively permeabilize the basolateral
membrane and thereby isolate the apical membrane
Ca2+-activated Cl current. In
P2X7-R-permeabilized cells, we have demonstrated that UTP
stimulates a Cl current across the apical membrane of CF
and normal murine tracheal epithelial cells. The magnitude of the
UTP-stimulated current was significantly greater in CF than in normal
cells. Ion substitution studies demonstrated that the current exhibited
a permselectivity sequence of Cl > I > Br > gluconate. We have
also determined a rank order of potency for putative Cl
channel blockers: niflumic acid 
5-nitro-2-(3-phenylpropylamino)benzoic acid > 4,4'-diisothiocyanostilbene-2,2'-disulfonate > glybenclamide 
diphenlyamine-2-carboxylate, tamoxifen, and
p-tetra-sulfonato-tetra-methoxy-calix[4]arene. Complete characterization of this current and the corresponding single
channel properties could lead to the development of a new therapy to
correct the defective airway surface liquid in cystic fibrosis patients.
*
This work was supported by Grant 99PO from the Cystic
Fibrosis Foundation and Grant HL62564 from the National Institutes of Health (both to S. E. G.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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