ROLE OF CA2-ACTIVATED K+ CHANNEL IN EPITHELIUM-DEPENDENT RELAXATION OF HUMAN BRONCHIAL SMOOTH-MUSCLE()

1 To elucidate whether K+ channels play a role in the action of epithe lium-dependent bronchodilatation, we studied responses in human bronch ial strips in the presence of indomethacin and N-G-nitro-L-argnine met hylester under isometric conditions, in vitro. 2 Mechanical removal of the epithelium increased the contractile responses to acetylcholine; the pD(2) values increased from 5.0+/-0.2 to 5.9+/-0.3 (P<0.001). This potentiation was abolished by iberiotoxin but not by apamin or gliben clamide. 3 In cascade bioassay, application of the bathing medium from dispersed, bronchial epithelial cells to epithelium-denuded bronchial strips decreased acetylcholine-induced contraction by 44+/-6%. This e ffect was reduced to 10+/-3% (P<0.01) when the epithelial cells were p retreated with iberiotoxin. and to 4+/-1% (P<0.001) when the epithelia l cells were incubated with Ca2+-free medium containing [1,2-bis (2) a minophenoxy] ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester. 4 I n contrast, the bronchodilator effect of the medium bathing epithelial cells was not altered by the direct addition of iberiotoxin to epithe lium-denuded tissues. 5 These results suggest that the Ca2+-activated K+ channel may play a role in the synthesis and/or release of smooth m uscle relaxing factor, which is neither nitric oxide nor a cyclo-oxyge nase product, from airway epithelial cells.