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

Leydon, Ciara; Fisher, Kimberly V.; Lodewyck-Falciglia, Danielle
June 2009
Journal of Speech, Language & Hearing Research;Jun2009, Vol. 52 Issue 3, p745
Academic Journal
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 randomize 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 (Isc; n = 10). Th secretagogue, isobutylmethylxanthine, yielded a 31.7% increase in mean Isc (n = 10 Another secretagogue, uridine triphosphate, elicited a 48.8% immediate and 17.3% sustained increase in mean Isc (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.


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