[Mucoviscidosis--3 years after discovery of the gene]

The discovery of the cystic fibrosis (cF) gene was the first step to evaluate the function of its product, the "cystic fibrosis transmembrane conductance regulator" protein and the regulation of this gene. CFTR is a cAMP-dependent CI(-)-channel, which is defect in cF. In contrast, a second CI(-)-channel in epithelial cells is activated by increasing intracellular Ca++ and fully functional in cF cells. Increasing intracellular Ca++ not only activates the Ca(++)-dependent channel, but also downregulates the CFTR gene expression in the same epithelial cells, suggesting a feedback mechanism. This regulatory pathway is based on a protein kinase, probably protein kinase C. The results of this study are a prerequisite for a gene therapy in cF which demands intimate knowledge of the regulation of the CFTR gene. In addition, these results suggest different therapeutical strategies to circumvent the defect in cF cells, which is discussed in detail.