Phosphorylation Fails to Activate Chloride Channels from Cystic Fibrosis Airway CellsNature
AbstractChloride impermeability of epithelial cells can account for many of the experimental and clinical manifestations of cystic fibrosis (CF)1,2. Activation of apical-membrane Cl− channels by cyclic AMP-mediated stimuli is defective in CF airway epithelial cells3,4, despite normal agonist-induced increases in cellular cAMP levels4,5. This defect in Cl− channel regulation has been localized to the apical membrane by exposing the cytoplasmic surface of excised membrane patches to the catalytic subunit (C subunit) of cAMP-dependent protein kinase and ATP. In membranes from normal cells, C-subunit activated Cl− channels with properties identical to those stimulated by cAMP-dependent agonists during cell-attached recording. Activation by the C subunit was not observed in CF membranes, but the presence of Cl− channels was verified by voltage-induced activation. The failure of the C subunit to activate the Cl− channels of CF membranes indicates that the block in their cAMP-mediated activation lies distal to induction of cAMP-dependent protein kinase activity and focuses our attention on the Cl− channel and its membrane-associated regulatory proteins as the probable site of the CF defect.
Citation InformationRobert A. Schoumacher, Richard L. Shoemaker, Dan R. Halm, E. Ann Tallant, et al.. "Phosphorylation Fails to Activate Chloride Channels from Cystic Fibrosis Airway Cells" Nature Vol. 330 (1987) p. 752 - 754 ISSN: 00280836
Available at: http://works.bepress.com/dan_halm/49/