CFTR and Cystic Fibrosis

The cystic fibrosis transmembrane conductance regulator (CFTR) is an essential anion channel that regulates fluid and electrolyte transport across a variety of epithelia. Mutations that reduce CFTR protein expression or channel activity cause cystic fibrosis, the most common lethal recessive genetic disorder among Caucasians. CFTR occupies a prominent position among ion channels, as physiologic investigation of genotype/phenotype correlation has led to significant biomedical advancement with direct consequence on quality of life and survival. Here, we review our current understanding of how CFTR functions as an ATP-gated and phosphorylation-regulated anion channel that is the only identified ion channel in the large superfamily of ATP-binding cassette (ABC) transporters. The CFTR gating mechanism is also compared to the gating mechanisms of other more conventional ligand-gated channels with an interpretation of how prospective drugs may affect channel function. The various mechanisms by which different classes of CFTR mutations disrupt the function of this anion channel to cause cystic fibrosis are also discussed. Finally, we review the clinical manifestations of cystic fibrosis disease and current treatment options with an emphasis on the recent development of drugs that directly target the basic anion channel defect.