Defective regulation of outwardly rectifying Cl− channels by protein kinase A corrected by insertion of CFTR
- 1 August 1992
- journal article
- Published by Springer Nature in Nature
- Vol. 358 (6387) , 581-584
- https://doi.org/10.1038/358581a0
Abstract
Cystic fibrosis (CF) is a lethal genetic disease resulting in a reduced Cl- permeability, increased mucous sulphation, increased Na+ absorption and defective acidification of lysosomal vesicles. The CF gene encodes a protein (the cystic fibrosis transmembrane conductance regulator, CFTR) that can function as a low-conductance Cl- channel with a linear current-voltage relationship whose regulation is defective in CF patients. Larger conductance, outwardly rectifying Cl- channels are also defective in CF and fail to activate when exposed either to cyclic AMP-dependent protein kinase A or to protein kinase C. The role of the outwardly rectifying Cl- channel in CF has been questioned. We report here that expression of recombinant CF genes using adeno-associated virus vectors in CF bronchial epithelial cells corrects defective Cl- secretion, that it induces the appearance of small, linear conductance Cl- channels, and restores protein kinase A activation of outwardly rectifying Cl- channels. These results re-establish an involvement of outwardly rectifying Cl- channels in CF and suggest that CFTR regulates more than one conductance pathway in airway tissues.Keywords
This publication has 21 references indexed in Scilit:
- Demonstration That CFTR Is a Chloride Channel by Alteration of Its Anion SelectivityScience, 1991
- Defective acidification of intracellular organelles in cystic fibrosisNature, 1991
- Expression of the cystic fibrosis gene in non-epithelial invertebrate cells produces a regulated anion conductanceCell, 1991
- Cystic fibrosis: a disease in electrolyte transportThe FASEB Journal, 1990
- Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNAScience, 1989
- Increased sulfation of glycoconjugates by cultured nasal epithelial cells from patients with cystic fibrosis.Journal of Clinical Investigation, 1989
- Regulation of Chloride Channels by Protein Kinase C in Normal and Cystic Fibrosis Airway EpitheliaScience, 1989
- Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epitheliumNature, 1988
- Phosphorylation fails to activate chloride channels from cystic fibrosis airway cellsNature, 1987
- Cystic Fibrosis: a disease of ion channels?Trends in Neurosciences, 1987