Role of Ca2+-activated K+ channel in epithelium-dependent relaxation of human bronchial smooth muscle

摘要

class="enumerated" style="list-style-type:decimal">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-arginine methylester under isometric conditions, in vitro.Mechanical removal of the epithelium increased the contractile responses to acetylcholine; the pD2 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.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.In contrast, the bronchodilator effect of the medium bathing epithelial cells was not altered by the direct addition of iberiotoxin to epithelium-denuded tissues.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.