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

Kimberly V. Fisher
Northwestern University, Evanston, IL

Danielle Lodewyck-Falciglia
New York University School of Medicine

Contact author: Ciara Leydon, Department of Speech Communication Arts and Sciences, Brooklyn College of The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210. E-mail: cleydon{at}brooklyn.cuny.edu.

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.

KEY WORDS: voice, vocal fold hydration, epithelium, transepithelial transport, chloride transport

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