Phosphorylation‐activated chloride channels in human skin fibroblasts

Abstract

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