Asthma prophylaxis agents alter the function of an airway epithelial chloride channel.
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.
Alton
E W
EW
Ion Transport Unit, Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
Kingsleigh-Smith
D J
DJ
Munkonge
F M
FM
Smith
S N
SN
Lindsay
A R
AR
Gruenert
D C
DC
Jeffery
P K
PK
Norris
A
A
Geddes
D M
DM
Williams
A J
AJ
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
D018927:Anti-Asthmatic Agents; D018118:Chloride Channels; D017835:Nedocromil; D005665:Furosemide; D004205:Cromolyn Sodium; D002118:Calcium