Is cystic fibrosis transmembrane conductance regulator (CFTR) a chloride channel or a chloride pump?

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the superfamily of ATP-binding cassette (ABC) transporters. It is located primarily in the apical membrane of epithelial cells, including airway, intestine, pancreas and sweat duct, which plays a critical role in epithelial ion-transport and fluid homeostasis. Mutation of CFTR can lead to cystic fibrosis which is an all-too-common genetic disease among Caucasians. Interestingly, CFTR has the structure of an ABC transporter, but it behaves in most ways like an anion channel. Many publications have stated that CFTR is an ATP-gated chloride channel, which is open or closed stochastically depending on ATP binding. In recent years, researchers have had a second thought about this topic and proposed that CFTR is a “leaky” chloride pump. Here, we bring together the latest information about the structure and function of CFTR, intending to clarify this phenomenon.