The cystic fibrosis transmembrane conductance regulator and chloride-dependent ion fluxes of ovine vocal fold epithelium.
OBJECTIVE
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.


METHODS
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.
Leydon
Ciara
C
Department of Speech Communication Arts and Sciences, Brooklyn College of The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA. cleydon@brooklyn.cuny.edu
Fisher
Kimberly V
KV
Lodewyck-Falciglia
Danielle
D
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D017136:Ion Transport; D007820:Laryngeal Mucosa / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D018408:Patch-Clamp Techniques; D010634:Phenobarbital / Q000494:pharmacology; D012756:Sheep; D026941:Sodium Channel Blockers / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014827:Vocal Cords / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D026941:Sodium Channel Blockers; D062367:ortho-Aminobenzoates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; C001209:fenamic acid; D015056:1-Methyl-3-isobutylxanthine; D014544:Uridine Triphosphate; D010634:Phenobarbital