title: Asthma prophylaxis agents alter the function of an airway epithelial chloride channel.
abstract: A number of recent observations suggest a link between airway Cl-transport and asthma. We have previously described the properties of a voltage- and Ca2+ -dependent chloride channel present in airway epithelium. We now show that agents able to prevent indirectly induced bronchoconstriction (sodium cromoglycate, nedocromil sodium, and furosemide) reduce either the single-channel conductance or the open probability of this channel. The effects of these agents and the Ca2+ dependence of the channel are localized to the same surface, and we show that the channel possesses a specific divalent cation binding site, which responds to concentrations of Ca2+ found on the airway mucosal surface. No alteration of the single-channel properties of this channel were seen in cystic fibrosis epithelium. These data suggest a mechanism by which structurally diverse agents may influence asthma.
authors.affiliation: Ion Transport Unit, Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
authors.forename: E W
authors.initials: EW
authors.lastname: Alton
authors.forename: D J
authors.initials: DJ
authors.lastname: Kingsleigh-Smith
authors.forename: F M
authors.initials: FM
authors.lastname: Munkonge
authors.forename: S N
authors.initials: SN
authors.lastname: Smith
authors.forename: A R
authors.initials: AR
authors.lastname: Lindsay
authors.forename: D C
authors.initials: DC
authors.lastname: Gruenert
authors.forename: P K
authors.initials: PK
authors.lastname: Jeffery
authors.forename: A
authors.initials: A
authors.lastname: Norris
authors.forename: D M
authors.initials: DM
authors.lastname: Geddes
authors.forename: A J
authors.initials: AJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000503:physiopathology; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D017835:Nedocromil / Q000494:pharmacology; D051381:Rats; D012756:Sheep
chemical_list: D018927:Anti-Asthmatic Agents; D018118:Chloride Channels; D017835:Nedocromil; D005665:Furosemide; D004205:Cromolyn Sodium; D002118:Calcium