Identification of a defective cAMP-stimulated Cl- channel in cystic fibrosis fibroblasts.

P Y Lin,E Gruenstein

doi:10.1016/s0021-9258(18)47730-7

P Y Lin, E Gruenstein

Open Access

https://doi.org/10.1016/s0021-9258(18)47730-7

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Abstract

Cl- efflux from normal human fibroblasts is stimulated by elevation of cAMP and by elevation of intracellular free Ca2+. In both cases the stimulated Cl- transport occurs via electrically conductive pathways. In six lines of normal human fibroblasts, dibutyryl cAMP increased total Cl- efflux by an average of 13%. In six lines of fibroblasts from patients with cystic fibrosis, dibutyryl cAMP was without effect. The electrically conductive component of Cl- transport was increased an average of 30% by dibutyryl cAMP in normal cells and was unaffected by dibutyryl cAMP in cystic fibrosis cells. Stimulation of the Ca2+-sensitive Cl- channel by addition of A23187 increased Cl- efflux by an average of 30% in normal and 30% in cystic fibrosis fibroblasts. The data indicate that there is a defect in a cAMP-activated Cl- channel in cystic fibrosis fibroblasts.

Highlights

CellCulture-Cystic fibrosis fibroblast lines GM997, GM 1957, From the Departmentof Biochemistry and Molecular Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
GM 1959,GM 3466,GM 4320, and GM 4339and age-matched normal control fibroblast lines GM 302, GM 2938A, GM 2987,and GM 3348 were obtained from the Institutefor Medical Research (Camden, NJ)
In six lines of fibroblastsfrom patients with cystic fibrosis, dibutyryl cAMP was without effect

Summary

Introduction

CellCulture-Cystic fibrosis fibroblast lines GM997, GM 1957, From the Departmentof Biochemistry and Molecular Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267. C1- efflux from normal human fibroblasts is stimulated by elevation of cAMP and by elevation of intracellular free Ca2+.Inboth cases thestimulated C1-

Results

Conclusion