Consequences of mutation and variable expression on functions of the cystic fibrosis transmembrane conductance regulator

Cystic fibrosis (CF), a life-limiting disorder of electrolyte transport manifest in the lungs, pancreas, sweat duct, and vas deferens, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR functions as a cAMP-activated chloride channel and regulates the function of another anion channel, the outwardly rectifying chloride channel (ORCC). The role of the regulatory function of CFTR is not known. In the first study, CFTR bearing a mutation associated with mild lung disease was shown to retain its ability to regulate the ORCC, while a mutation associated with severe lung disease abolished this function. Thus, dysregulation of the ORCC may play a role in CF lung disease. My next studies further explored this concept. To determine whether a threshold level of CFTR needs to be present for activation of the ORCC, the level of CFTR expression was determined in three normal airway epithelial cell lines and correlated with electrophysiologic studies of cAMP-activated Cl...