The Cystic Fibrosis Transmembrane Conductance Regulator and Chloride-Dependent Ion Fluxes of Ovine Vocal Fold Epithelium

Abstract

Purpose Ion-driven transepithelial water fluxes participate in maintaining superficial vocal fold hydration, which is necessary for normal voice production. The authors hypothesized that Cl − channels are present in vocal fold epithelial cells and that transepithelial Cl − fluxes can be manipulated pharmacologically. Method Immunohistochemical assays were used to identify cystic fibrosis transmembrane regulator Cl − channels in ovine vocal fold mucosae ( n = 2). Electrophysiological responses of vocal fold mucosae ( n = 80) to Cl − channel inhibitors and secretagogues were evaluated in an ovine model using a randomized controlled experimental design. Results Cystic fibrosis transmembrane regulator channels were localized to the plasma membranes of epithelial cells. The Cl − transport inhibitor, diphenylamine-2-carboxylate, elicited a 30% decrease in mean short-circuit current (I sc ; n = 10). The secretagogue, isobutylmethylxanthine, yielded a 31.7% increase in mean I sc ( n = 10). Another secretagogue, uridine triphosphate, elicited a 48.8% immediate and 17.3% sustained increase in mean I sc ( n = 10). No sustained increases occurred following application of secretagogues to mucosae bathed in a low Cl − environment ( n = 10), suggesting that responses were Cl − dependent. Conclusions The authors provide structural and functional evidence for the presence of a transepithelial pathway for Cl − fluxes. Pharmacological manipulation of this pathway may offer a mechanism for maintaining superficial vocal fold hydration.