ELECTRODIFFUSIONAL ATP MOVEMENT THROUGH THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

Expression of the cystic fibrosis transmembrane conductance regulator (CFTR), and of at least one other member of the ATP-binding cassette f amily of transport proteins, P-glycoprotein, is associated with the el ectrodiffusional movement of the nucleotide ATP. Evidence directly imp licating CFTR expression with ATP channel activity, however, is still missing. Here it is reported that reconstitution into a lipid bilayer of highly purified CFTR of human epithelial origin enables the permeat ion of bath Cl- and ATP. Similar to previously reported data for in vi vo ATP currents of CFTR-expressing cells, the reconstituted channels d isplayed competition between Cl- and ATP and had multiple conductance states in the presence of Cl- and ATP. Purified CFTR-mediated ATP curr ents were activated by protein kinase A and ATP (1 mM) from the ''intr acellular'' side of the molecule and were inhibited by diphenylamine-2 -carboxylate, glibenclamide, and anti-CFTR antibodies. The absence of CFTR-mediated electrodiffusional ATP movement may thus be a relevant c omponent of the pleiotropic cystic fibrosis phenotype.