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.