Function of ion channels of epithelial cells in cystic fibrosis

Abstract

Cystic fibrosis is a systemic hereditary disease caused by mutations in the CFTR gene, which regulates the transport of electrolytes (mainly chloride) across the membranes of the epithelial cells that line excretory ducts of exocrine glands. Dysfunction of the CFTR protein reduces passage of chloride ions through cell membranes and disrupts the passage of sodium ions, bicarbonate ions, and water.The aim of the study was to analyze comprehensively functioning of chloride and alternative (sodium and calcium) channels in the epithelium of patients with cystic fibrosis in relation to the age using functional tests in vitro.Methods. We used data from medical histories of patients with cystic fibrosis and intestinal current measurements.Results. The function of the calcium channel decreased with age in people without cystic fibrosis and carriers of “severe” genotypes. The function of sodium, chloride, and calcium channels was lower in all age groups of patients with cystic fibrosis compared to controls (p < 0.05). When comparing groups of patients with “severe genotype” and “mild genotype”, statistically significant differences were found in response to forskolin (p < 0.05). Patients with “mild” genotypes had a residual function of the CFTR channel which decreased with age.Conclusion. For the first time, the functioning of chloride and alternative channels in cystic fibrosis have been described in relation to the age and the genotype of patients.