Chapter 29 - The Cystic Fibrosis Transmembrane Conductance Regulator (ABCC7)

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) is the product of the gene mutated in patients with cystic fibrosis (CF), an autosomal recessive disease of relatively high frequency in the Caucasian population. The absence or dysfunction of CFTR results in aberrant ion and liquid homeostasis at epithelial surfaces of the respiratory, intestinal, and reproductive tracts as well as other secretory and reabsorptive epithelia. CFTR is a channel that allows anions to diffuse through the membrane in either direction (absorptive or secretory) depending on the electrochemical gradients. Since chloride is the predominant inorganic anion in vivo, the CFTR pore conducts mainly Cl- ions under physiological conditions, although significant bicarbonate transport may also occur in some tissues. Cl- ions move out of the cell through apical CFTR channels, which are the rate-limiting step during secretion. Indeed, the crucial role that the CFTR chloride channel plays in fluid secretion in the intestine may be at the basis of the so-called “heterozygote advantage”, which could account for the relatively high mutant gene frequency despite the fact that the mutations are generally not propagated by homozygotes.