Increased Sensitivity of Porcine ΔF508-CFTR Chloride Channel to Specific Small Molecule CFTR Inhibitors

Deletion of the codon encoding the phenylalanine residue at position 508（ΔF508） in the cystic fibrosis transmembrane conductance regulator（CFTR） is the most common mutation causing cystic fibrosis（CF）.The human ΔF508 mutation results in a CFTR protein with impaired folding,trafficking,and gating in human and rodents.Recent studies suggest that pig ΔF508-CFTR can be efficiently processed to the plasma membrane as maturely glycosylated protein,indicating species difference of the molecular mechanisms of CFTR cellular maturation.In this study,the functional characterization in stably transfected FRT cells cultured at 37 ℃ demonstrates that pig ΔF508-CFTR is remarkably more sensitive to specific CFTR inhibitors CFTRinh-172 and GlyH101 than wildtype pig CFTR.The wildtype pig CFTR is more sensitive to GlyH101 than to CFTRinh-172.The present study indicates that the gating property of ΔF508-CFTR chloride channel is altered and GlyH101 may be a more suitable small molecule probe for generating CF phenotypes in pig tissues.