The Cystic Fibrosis Transmembrane Conductance Regulator and Chloride-Dependent Ion Fluxes of Ovine Vocal Fold Epithelium 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 ... Research Article
Research Article  |   June 01, 2009
The Cystic Fibrosis Transmembrane Conductance Regulator and Chloride-Dependent Ion Fluxes of Ovine Vocal Fold Epithelium
 
Author Affiliations & Notes
  • Ciara Leydon
    Brooklyn College of The City University of New York
  • 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@brooklyn.cuny.edu.
Article Information
Speech, Voice & Prosody / Speech / Research Articles
Research Article   |   June 01, 2009
The Cystic Fibrosis Transmembrane Conductance Regulator and Chloride-Dependent Ion Fluxes of Ovine Vocal Fold Epithelium
Journal of Speech, Language, and Hearing Research, June 2009, Vol. 52, 745-754. doi:10.1044/1092-4388(2008/07-0192)
History: Received August 17, 2007 , Revised February 18, 2008 , Accepted July 18, 2008
 
Journal of Speech, Language, and Hearing Research, June 2009, Vol. 52, 745-754. doi:10.1044/1092-4388(2008/07-0192)
History: Received August 17, 2007; Revised February 18, 2008; Accepted July 18, 2008
Web of Science® Times Cited: 3

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 (Isc; n = 10). The 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.

Acknowledgments
This research was supported by Grant K08-DC0068 from the National Institute on Deafness and Other Communication Disorders, awarded to the second author. This work was completed as a thesis by the first author submitted in partial fulfillment of the doctor of philosophy degree from the Department of Communication Sciences and Disorders at Northwestern University. We thank dissertation committee members Charles Larson and Jonathan Siegel for generously sharing their thoughtful insights into this work, and William Russin for his assistance with the immunohistochemical portion of the experiments. We also thank Christopher Atkins and Mahalaksmi Sivasankar for their invaluable assistance at all stages of this study and for their comments on earlier versions of this article.
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