Alton E W, Kingsleigh-Smith D J, Munkonge F M, Smith S N, Lindsay A R, Gruenert D C, Jeffery P K, Norris A, Geddes D M, Williams A J
Ion Transport Unit, Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
Am J Respir Cell Mol Biol. 1996 Apr;14(4):380-7. doi: 10.1165/ajrcmb.14.4.8600943.
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.
最近的一些观察结果表明气道氯离子转运与哮喘之间存在联系。我们之前已经描述了气道上皮细胞中存在的一种电压和钙离子依赖性氯离子通道的特性。我们现在表明，能够预防间接诱导支气管收缩的药物（色甘酸钠、奈多罗米钠和呋塞米）会降低该通道的单通道电导或开放概率。这些药物的作用以及通道对钙离子的依赖性定位于同一表面，并且我们表明该通道具有一个特定的二价阳离子结合位点，该位点对气道黏膜表面发现的钙离子浓度有反应。在囊性纤维化上皮细胞中未观察到该通道单通道特性的改变。这些数据提示了一种机制，通过该机制结构多样的药物可能影响哮喘。
