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PMID: 1371880 Published · ppublish English Journal Article

Regulation of Cl- channels in normal and cystic fibrosis airway epithelial cells by extracellular ATP.

Stutts MJ, Chinet TC, Mason SJ, Fullton JM, Clarke LL, Boucher RC

Abstract

The rate of Cl- secretion by human airway epithelium is determined, in part, by apical cell membrane Cl- conductance. In cystic fibrosis airway epithelia, defective regulation of Cl- conductance decreases the capability to secrete Cl-. Here we report that extracytosolic ATP in the luminal bath of cultured human airway epithelia increased transepithelial Cl- secretion and apical membrane Cl- permeability. Single-channel studies in excised membrane patches revealed that ATP increased the open probability of outward rectifying Cl- channels. The latter effect occurs through a receptor mechanism that requires no identified soluble second messengers and is insensitive to probes of G protein function. These results demonstrate a mode of regulation of anion channels by binding ATP at the extracellular surface. Regulation of Cl- conductance by external ATP is preserved in cystic fibrosis airway epithelia.

MeSH Terms
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid/analogs & derivatives,pharmacology Adenosine Triphosphate/physiology Cells, Cultured Chloride Channels Chlorides/physiology Cystic Fibrosis/physiopathology Electric Conductivity Epithelium/physiopathology Humans In Vitro Techniques Ion Channel Gating/drug effects Ion Channels/physiology Membrane Potentials Membrane Proteins/physiology Respiratory System/physiopathology
Chemicals
Chloride Channels Chlorides Ion Channels Membrane Proteins 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid Adenosine Triphosphate 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Stutts M J
Department of Medicine, University of North Carolina, Chapel Hill 27599-7020.
Chinet T C
Mason S J
Fullton J M
Clarke L L
Boucher R C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1992-03-01
Pages
1621-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48504
Subset
IM
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