Being positive: revisiting the elevated sodium permeability hypothesis in cystic fibrosis.
Being positive: revisiting the elevated sodium permeability hypothesis in cystic fibrosis.
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积极乐观：重新审视囊性纤维化中钠渗透性升高的假说。
DOI：
10.1113/jphysiol.2013.260406
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kirk,KevinL
中科院分区：
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作者：
Kirk,KevinL
囊性纤维化(CF)是一种由囊性纤维化跨膜电导调节(CFTR)阴离子通道突变引起的破坏性肺部疾病。CFTR通道活性降低会导致进入呼吸道的粘膜下腺分泌的盐和水有缺陷，并导致覆盖在呼吸道表面的薄液体层(呼吸道表面液体，或ASL)的组成和深度发生变化。ASL中的这些变化损害了粘液纤毛的清除，增加了对呼吸道细菌感染的易感性。25年来，人们一直认为CFTR功能障碍也会导致呼吸道表面上皮细胞顶端钠通透性的增加(Boucher等人)。(1988年)。钠渗透性的增加有望增强跨越呼吸道表面上皮细胞的盐和水的重吸收，并有助于ASL体积和粘液纤毛清除的减少。CFTR功能障碍如何导致心尖膜钠离子通透性升高尚不清楚，但可以想见，这可能涉及对这些细胞顶膜上皮钠离子通道(ENaCs)活性或数量的继发性影响。如果是真的，钠通透性假说暗示ENaC调节是治疗CF肺部疾病的潜在药物靶点。这一假设在很大程度上是基于阿米洛利，一种相当特异的ENaC抑制剂，与正常的呼吸道上皮相比，对CF的电特性有更大的影响，尤其是在
Cystic fibrosis (CF) is a devastating lung disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Reduced CFTR channel activity leads to defective salt and water secretion by the submucosal glands that empty into the airways and changes in the composition and depth of the thin fluid layer covering the airway surface (airway surface liquid, or ASL). These alterations in the ASL compromise mucociliary clearance and increase susceptibility to bacterial infections in the airways.For over 25years it has been argued that CFTR dysfunction also leads to an increase in the apical sodium permeabilities of epithelial cells on the airway surface (Boucher et al. 1988). An increase in sodium permeability would be expected to enhance salt and water reabsorption across airway surface epithelia and contribute to reductions in ASL volume and mucociliary clearance. How CFTR dysfunction might lead to enhanced apical sodium permeability is unknown but conceivably involves a secondary effect on the activities or numbers of epithelial sodium channels (ENaCs) in the apical membranes of these cells. If true, the sodium permeability hypothesis implicates ENaC regulation as a potential drug target for treating CF lung disease. The proposal that apical sodium permeability is elevated in CF airway epithelia is based largely on the finding that amiloride, a fairly specific ENaC inhibitor, has substantially greater effects on the electrical properties of CF versus normal airway epithelia, in particular on