Burch L H, Talbot C R, Knowles M R, Canessa C M, Rossier B C, Boucher R C
Department of Medicine, University of North Carolina at Chapel Hill 27599-7020, USA.
Am J Physiol. 1995 Aug;269(2 Pt 1):C511-8. doi: 10.1152/ajpcell.1995.269.2.C511.
The availability of the newly cloned subunits (alpha, beta, gamma) of the epithelial Na+ channel (ENaC) permits molecular studies of the pathogenesis of the abnormal Na+ transport rates of cystic fibrosis (CF) airway epithelia. Northern analyses of airway epithelia showed that both normal and CF airway epithelia express ENaC subunit mRNAs in a ratio of alpha > beta > gamma. In situ hybridization studies revealed expression of all three ENaC subunits in the superficial epithelium and the alpha- and beta-subunits in the gland ductular and acinar epithelium of both normal and CF airways. Ribonuclease protection assays revealed that the steady-state levels of alpha-, beta-, and gamma-ENaC mRNAs were similar in CF and normal airway superficial epithelia. These findings indicate that 1) Na+ transport defects in CF airways disease may be expressed in glandular acinar and ductal epithelium as well as superficial epithelium, and 2) the molecular pathogenesis of Na+ hyperabsorption in CF airways does not reflect increased levels of Na+ channel mRNAs, and probably number, but reflects an absence of the normal inhibitory regulation of Na+ channels by CF transmembrane conductance regulator proteins.
新克隆的上皮钠通道（ENaC）亚基（α、β、γ）的可得性使得对囊性纤维化（CF）气道上皮细胞异常钠转运速率发病机制进行分子研究成为可能。对气道上皮细胞的Northern分析表明，正常和CF气道上皮细胞均以α>β>γ的比例表达ENaC亚基mRNA。原位杂交研究显示，正常和CF气道的表层上皮细胞均表达所有三种ENaC亚基，腺导管和腺泡上皮细胞表达α-和β-亚基。核糖核酸酶保护试验显示，CF和正常气道表层上皮细胞中α-、β-和γ-ENaC mRNA的稳态水平相似。这些发现表明：1）CF气道疾病中的钠转运缺陷可能在腺泡、导管上皮细胞以及表层上皮细胞中表现出来；2）CF气道中钠过度吸收的分子发病机制并不反映钠通道mRNA水平的升高，可能也不反映其数量的增加，而是反映CF跨膜电导调节蛋白对钠通道缺乏正常的抑制调节。
