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 epithelium-dependent bronchodilatation, we studied responses in human bronchial strips in the presence of indomethacin and N-G-nitro-L-argnine methylester 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 glibenclamide. 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 effect was reduced to 10+/-3% (P<0.01) when the epithelial cells were pretreated with iberiotoxin. and to 4+/-1% (P<0.001) when the epithelial cells were incubated with Ca2+-free medium containing [1,2-bis (2) aminophenoxy] ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester. 4 In contrast, the bronchodilator effect of the medium bathing epithelial cells was not altered by the direct addition of iberiotoxin to epithelium-denuded tissues. 5 These results suggest that the Ca2+-activated K+ channel may play a role in the synthesis and/or release of smooth muscle relaxing factor, which is neither nitric oxide nor a cyclo-oxygenase product, from airway epithelial cells.