Kunzelmann K, Schreiber R, Nitschke R, Mall M
University of Sydney, Dept. of Physiology, NSW, Australia.
Pflugers Arch. 2000 Jun;440(2):193-201. doi: 10.1007/s004240000255.
Cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial Cl- channel expressed in luminal membranes of secretory and reabsorptive epithelia. CFTR plays a predominant role in both cAMP- and Ca2+-activated secretion of electrolytes. Although Ca2+-dependent Cl- channels exist independent of CFTR in the airway epithelium, their physiological significance remains to be determined. However, CFTR seems to be the only relevant Cl- conductance in the colonic epithelium. Apart from its secretory function, CFTR also has a task in regulating the reabsorption of electrolytes by controlling the activity of the epithelial Na+ channel, ENaC. Accordingly, defects in CFTR causing the disease cystic fibrosis (CF) lead to disturbances of both the secretion and absorption of electrolytes. Therefore, it is unclear what is pathophysiologically more important for the development of CF lung disease, the impaired secretion of Cl- or the enhanced reabsorption of Na+ and consecutive hyperabsorption of electrolytes. The mechanisms of how CFTR and ENaC interact are unknown. Previous work has given rise to several interesting working hypothesis, such as direct protein interaction or interaction via cytoskeletal proteins. Recent studies demonstrate the importance of the first nucleotide binding fold of CFTR, not only for the inhibition of ENaC but also for the interaction with other ion channels. Further studies are required to demonstrate whether regulation of other ion channels and membrane transport by CFTR occur by a common mechanism.
囊性纤维化跨膜传导调节因子（CFTR）是一种上皮细胞氯离子通道，表达于分泌性和重吸收性上皮细胞的管腔膜上。CFTR在cAMP和Ca2+激活的电解质分泌过程中起主要作用。虽然气道上皮细胞中存在不依赖CFTR的Ca2+依赖性氯离子通道，但其生理意义仍有待确定。然而，CFTR似乎是结肠上皮细胞中唯一相关的氯离子传导途径。除了其分泌功能外，CFTR还通过控制上皮钠离子通道ENaC的活性来调节电解质的重吸收。因此，导致囊性纤维化（CF）疾病的CFTR缺陷会导致电解质分泌和吸收的紊乱。因此，对于CF肺部疾病的发展，在病理生理学上尚不清楚是氯离子分泌受损还是钠离子重吸收增强以及随之而来的电解质过度吸收更为重要。CFTR和ENaC相互作用的机制尚不清楚。先前的研究提出了几个有趣的工作假设，如直接蛋白质相互作用或通过细胞骨架蛋白的相互作用。最近的研究表明CFTR的第一个核苷酸结合结构域不仅对ENaC的抑制很重要，而且对与其他离子通道的相互作用也很重要。还需要进一步的研究来证明CFTR对其他离子通道和膜转运的调节是否通过共同机制发生。
