Regulation of Cl- channels in normal and cystic fibrosis airway epithelial cells by extracellular ATP.
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.
Department of Medicine, University of North Carolina, Chapel Hill 27599-7020.
M J
MJ
Stutts
T C
TC
Chinet
S J
SJ
Mason
J M
JM
Fullton
L L
LL
Clarke
R C
RC
Boucher
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004553:Electric Conductivity; D004848:Epithelium / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000502:physiology*; D012137:Respiratory System / Q000503:physiopathology*
D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000255:Adenosine Triphosphate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid