ASTHMA PROPHYLAXIS AGENTS ALTER THE FUNCTION OF AN AIRWAY EPITHELIAL CHLORIDE CHANNEL

A number of recent observations suggest a link between airway Cl- tran sport and asthma. We have previously described the properties of a vol tage- and Ca2+-dependent chloride channel present in airway epithelium . We now show that agents able to prevent indirectly induced bronchoco nstriction (sodium cromoglycate, nedocromil sodium, and furosemide) re duce either the single-channel conductance or the open probability of this channel. The effects of these agents and the Ca2+ dependence of t he channel are localized to the same surface, and we show that the cha nnel possesses a specific divalent cation binding site, which responds to concentrations of Ca2+ found on the airway mucosal surface. No alt eration of the single-channel properties of this channel were seen in cystic fibrosis epithelium. These data suggest a mechanism by which st ructurally diverse agents may influence asthma.