TITLE

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

AUTHOR(S)
Leydon, Ciara; Fisher, Kimberly V.; Lodewyck-Falciglia, Danielle
PUB. DATE
June 2009
SOURCE
Journal of Speech, Language & Hearing Research;Jun2009, Vol. 52 Issue 3, p745
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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 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.
ACCESSION #
40305031

 

Related Articles

  • CFTR: A chloride channel, channel regulator, or both? Rossier, Bernard // Kidney International;Nov2002, Vol. 62 Issue 5, p1517 

    Discusses issues related to the structure, the function and the regulation of cystic fibrosis transmembrane conductance regulator (CFTR). Interaction between CFTR and the epithelial sodium channel; Role of CFTR in transepithelial sodium absorption in the ducts of sweat glands; Two main...

  • The biochemical defect in cystic fibrosis. Cuthbert, Alan W. // Journal of the Royal Society of Medicine (Supplement);Jan1992, Vol. 85 Issue 19, p2 

    The article discusses the protein coded for by the cystic fibrosis gene (CF) called the CF transmembrane conductance regulator (CFTR). It explains the studies that show the probability that CFTR is a chloride channel. It cites that the disease phenotype in cells can be remedied and introduced by...

  • TMEM16A-TMEM16B chimaeras to investigate the structure-function relationship of calcium-activated chloride channels. SCUDIERI, Paolo; SONDO, Elvira; CACI, Emanuela; RAVAZZOLO, Roberto; GALIETTA, Luis J. V. // Biochemical Journal;6/15/2013, Vol. 452 Issue 3, following p443 

    TMEM16A and TMEM16B proteins are CaCCs (Ca2+ -activated Cl- channels) with eight putative transmembrane segments. As shown previously, expression of TMEM16B generates CaCCs characterized by a 10-fold lower Ca2+ affinity and by faster activation and deactivation kinetics with respect to TMEM16A....

  • Multi-ion pore behaviour in the CFTR chloride channel. Tabcharani, Joseph A.; Rommens, Johanna M. // Nature;11/4/1993, Vol. 366 Issue 6450, p79 

    Presents evidence that wild-type cystic fibrosis transmembrane conductance regulator (CFTR) can contain more than one anion simultaneously. Anomalous mole fraction effect of the wild-type CFTR; Importance of two positively charged residues in the sixth predicted transmembrane segment; Mutation...

  • Genistein Modifies the Activation Kinetics and Magnitude of Phosphorylated Wild-Type and G551D-CFTR Chloride Currents. Bulteau-Pignoux, L.; Dérand, R.; Métayé, T.; Joffre, M.; Becq, F. // Journal of Membrane Biology;Aug2002, Vol. 188 Issue 3, p175 

    We have studied the mechanism by which genistein activates cystic fibrosis transmembrane conductance regulator (CFTR) in CHO cells expressing wild type or G551D-CFTR. In wild-type CHO cells, after exposure to 2.5 mM forskolin, 25 mM genistein induced a further 2-fold and rapid increase of the...

  • Thiocyanate as a probe of the cystic fibrosis transmembrane conductance regulator chloride channel pore. Linsdell, Paul // Canadian Journal of Physiology & Pharmacology;Jul2001, Vol. 79 Issue 7, p573 

    Immediately following exposure to thiocyanate (SCN[sup –] )-containing solutions, the cystic fibrosis conductance regulator Cl[sup –] channel exhibits high unitary SCN[sup –] conductance and anomalous mole fraction behaviour, suggesting the presence of multiple anion binding...

  • CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Di, Anke; Brown, Mary E.; Deriy, Ludmila V.; Chunying Li; Szeto, Frances L.; Yimei Chen; Huang, Ping; Tong, Jiankun; Naren, Anjaparavanda P.; Bindokas, Vytautas; Palfrey, H. Clive; Nelson, Deborah J. // Nature Cell Biology;Sep2006, Vol. 8 Issue 9, p933 

    Acidification of phagosomes has been proposed to have a key role in the microbicidal function of phagocytes. Here, we show that in alveolar macrophages the cystic fibrosis transmembrane conductance regulator Cl− channel (CFTR) participates in phagosomal pH control and has bacterial killing...

  • Molecular models of the open and closed states of the whole human CFTR protein. Mornon, Jean-Paul; Lehn, Pierre; Callebaut, Isabelle // Cellular & Molecular Life Sciences;Nov2009, Vol. 66 Issue 21, p3469 

    Cystic fibrosis transmembrane conductance regulator (CFTR), involved in cystic fibrosis (CF), is a chloride channel belonging to the ATP-binding cassette (ABC) superfamily. Using the experimental structure of Sav1866 as template, we previously modeled the human CFTR structure, including...

  • Regulation of CFTR chloride channels by syntaxin and Munc 18 isoforms. Naren, Anjaparavanda P; Nelson, Deborah J. // Nature;11/20/1997, Vol. 390 Issue 6657, p302 

    Discusses research that showed that a cyclic AMP-gated chloride channel (CFTR) is regulated by an epithelially expressed syntaxin (syntaxin 1A). Encoding by the cystic fibrosis gene; Role of CFTR; Details about syntaxin 1A; Interactions between syntaxin 1A and CFTR; Implications of results.

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics