Permeation through the CFTR chloride channel

The cystic fibrosis transmembrane conductance regulator (CFTR) protein form s a Cl- channel found in the plasma membranes of many epithelial cells, inc luding those of the kidney, gut and conducting airways. Mutation of the gen e encoding CFTR is the primary defect in cystic fibrosis, a disease that af fects approximately 30 000 individuals in the United States alone. Alterati on of CFTR function also plays an important role in the pathophysiology of secretory diarrhea and polycystic kidney disease. The basic mechanisms of p ermeation in this channel are not well understood. It is not known which po rtions of the protein contribute to forming the pore or which amino acid re sidues in those domains are involved in the biophysical processes of ion pe rmeation. In this review, I will discuss (i) the present understanding of i on transport processes in the wild-type CFTR channel, (ii) the experimental approaches currently being applied to investigate the pore, and (iii) a pr oposed structure that takes into account the present data on mechanisms of ion selectivity in the CFTR channel and on blockade of the pore by open-cha nnel blockers.