FAILURE OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR TOCONDUCT ATP

The cystic fibrosis transmembrane conductance regulator (CFTR) is a ch loride ion channel regulated by protein kinase A and adenosine triphos phate (ATP). Loss of CFTR-mediated chloride ion conductance from the a pical plasma membrane of epithelial cells is a primary physiological l esion in cystic fibrosis. CFTR has also been suggested to function as an ATP channel, although the size of the ATP anion is much larger than the estimated size of the CFTR pore. ATP was not conducted through CF TR in intact organs, polarized human lung cell lines, stably transfect ed mammalian cell lines, or planar lipid bilayers reconstituted with C FTR protein. These findings suggest that ATP permeation through the CF TR is unlikely to contribute to the normal function of CFTR or to the pathogenesis of cystic fibrosis.