Phosphorylation-activated chloride channels in human skin fibroblasts.
A chloride-selective channel has been found using patch-clamp electrophysiology in human skin fibroblasts and it exhibits many of the biophysical properties of the Cl- channel found in airway epithelia. As in the case of epithelial Cl- channels, Cl- channels in fibroblasts are activated at depolarized membrane potentials in excised patches, rectifying in an outward direction with a unit conductance of 33 pS at 0 mV. Furthermore, the agonists forskolin and prostaglandin E2 evoke Cl- channel activity in cell-attached patches. The effect of these agonists can be mimicked by direct application of catalytic subunit of protein kinase A with ATP and Mg2+ to the internal membrane surface of excised, inside-out patches. The Cl- channel is also sensitive to inhibition by the stilbene derivative, DIDS. These results indicate that fibroblasts may provide a convenient and available model for the study of epithelial Cl- channel regulation and accelerate efforts to determine the regulatory defect expressed in cystic fibrosis.
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Department of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D012879:Skin Physiological Phenomena
D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D005576:Colforsin; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D011494:Protein Kinases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid