Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function
Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function
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DOI：
10.1038/46297
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发表时间：
1999-11-18
期刊：
影响因子：
64.8
通讯作者：
Quinton, PM
中科院分区：
文献类型：
--
作者：
Reddy, MM;Light, MJ;Quinton, PM
越来越多的人认识到，细胞协调不同离子通道的活动，使电解质进入细胞。然而，在致死性遗传性疾病囊性纤维化中出现了一个令人困惑的通道调节问题，这是由于上皮细胞膜中特异性Cl-通道（CFTR通道）的丢失(1)。尽管这种缺陷明显抑制了汗腺对Na+的吸收（2,3），但人们普遍认为，囊性纤维化患者有缺陷的气道中Na+的吸收异常升高（4,5）。唯一经常被引用的对这种超转运的解释是上皮Na+通道（ENaC）的活性与CFTR Cl-通道的活性呈负相关（5-7）。然而，我们在这里报道，在新鲜分离的正常汗管中，ENaC活性依赖于CFTR活性，并随着CFTR活性的增加而增加。令人惊讶的是，我们还发现囊性纤维化中Cl-通透性的主要缺陷(8)伴随着该组织中不能被激活的Na+电导。因此，囊性纤维化中盐吸收的减少不仅是由于Cl-电导率差，而且是由于Na+电导率差。
It is increasingly being recognized that cells coordinate the activity Of separate ion channels that allow electrolytes into the cell. However, a perplexing problem in channel regulation has arisen in the fatal genetic disease cystic fibrosis, which results fi om the loss of a specific Cl- channel (the CFTR channel) in epithelial cell membranes(1). Although this defect clearly inhibits the absorption of Na+ in sweat gands(2,3), it is widely accepted that Na+ absorption is abnormally elevated in defective airways in cystic fibrosis(4,5). The only frequently cited explanation for this hypertransport is that the activity of an epithelial Na+ channel (ENaC) is inversely related to the activity of the CFTR Cl- channel(5-7). However we report here that, in freshly isolated normal sweat ducts, ENaC activity is dependent on, and increases with, CFTR activity. Surprisingly, we also find that the primary defect in Cl- permeability in cystic fibrosis(8) is accompanied secondarily by a Na+ conductance in this tissue that cannot: be activated. Thus, reduced salt absorption in cystic fibrosis is due not only to poor Cl- conductance but also to poor Na+ conductance.