Am. J. Respir. Cell Mol. Biol., Vol 14, No. 4, 04 1996, 380-387.
Asthma prophylaxis agents alter the function of an airway epithelial chloride channel
EW Alton, DJ Kingsleigh-Smith, FM Munkonge, SN Smith, AR Lindsay, DC Gruenert, PK Jeffery, A Norris, DM Geddes and AJ Williams
Ion Transport Unit, Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
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.
