Submucosal gland ion channels and cystic fibrosis.

Abstract

Cystic fibrosis (CF), the most common fatal genetic disease, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) [20, 22]. Since the CFTR gene was identified in 1989 [23], a lot of research effort has been focused on either replacing the defective gene or rescuing the function of mutant CFTR in CF patients [20, 22]. Overall, no currently approved treatment cures the disease [22]. Most of the morbidity and mortality of CF results from lung disease which involves devastating loss of transepithelial anion secretion [20, 28, 29]. In lung, CFTR is strongly expressed in submucosal glands, it has been suggested that these cells represent the primary site of cystic fibrosis pathology [1, 2]. Anion secretion in submucosal gland is mediated by CFTR cr channels at the apical membrane [4], however, other chloride channels may also involves and the net rate of secretion is determined by the activity of basolateral K+ channels.