Altered chloride metabolism in cultured cystic fibrosis skin fibroblasts

An abnormal regulation of chloride permeability has been described for epithelial cells from patients with cystic fibrosis (CF). To learn more about the biochemical basis of this inherited disease, we have studied chloride metabolism in cultured CF fibroblasts by comparing the efflux of ³⁶Cl^- from matched pairs of CF and normal fibroblasts. The rate constants describing ³⁶Cl^- efflux did not differ between the two cell types, but in each of the four pairs tested the amount of ³⁶Cl^- contained within CF cells was consistently reduced, by 25-30%, relative to normal cells. Comparisons of cell water content and ²²Na⁺ efflux showed no differences between the two cell types, suggesting that overall intracellular chloride concentration is lower than normal in CF fibroblasts. Such data suggest that the CF gene defect is expressed in skin fibroblasts and that this defect may alter the regulation of intracellular Cl^- concentration, perhaps through changes in Cl^- permeability.