THE CFTR CHLORIDE CHANNEL

Cystic fibrosis transmembrane conductance regulator (CFTR) appears to be the first identified member of a novel class of Cl channels. CFTR is a regulated Cl− channel located in the apical membrane of several Cl− secretory epithelia. Regulation of CFTR is complex and involves both phosphorylation and an interaction with intracellular nucleotides. The combination of a molecular biologic approach (using site-directed mutagenesis and expression of CFTR in heterologous cells), a biochemical approach (using CFTR-specific antibodies), and an electrophysiologic approach (using the patch-clamp technique) is beginning to provide essential information about the structure and function of the various domains of this interesting channel. CFTR is regulated by phosphorylation of the R domain. First, addition of cyclic adenosine monophosphate (cAMP) agonists increases the apical membrane Cl− permeability of normal, but not CF, epithelia, and addition of cAMP agonists activates CFTR Cl− channels in heterologous cells, expressing recombinant CFTR. The biophysical properties of recombinant CFTR Cl− channels are the same as those of endogenous CFTR Cl− channels. Under baseline conditions, there is little, if any, Cl− current in cells endogenously, expressing CFTR. Following the addition of cAMP agonists, there is a dramatic increase in Cl− current in both whole-cell patch-clamp studies in individual epithelial cells. Cl− channel activation does not occur in response to an increase in intracellular Ca2+. © 1994 Academic Press, Inc.