Stutts M J, Canessa C M, Olsen J C, Hamrick M, Cohn J A, Rossier B C, Boucher R C
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill 27599-7020, USA.
Science. 1995 Aug 11;269(5225):847-50. doi: 10.1126/science.7543698.
Cystic fibrosis transmembrane regulator (CFTR), the gene product that is mutated in cystic fibrosis (CF) patients, has a well-recognized function as a cyclic adenosine 3',5'-monophosphate (cAMP)-regulated chloride channel, but this property does not account for the abnormally high basal rate and cAMP sensitivity of sodium ion absorption in CF airway epithelia. Expression of complementary DNAs for rat epithelial Na+ channel (rENaC) alone in Madin Darby canine kidney (MDCK) epithelial cells generated large amiloride-sensitive sodium currents that were stimulated by cAMP, whereas coexpression of human CFTR with rENaC generated smaller basal sodium currents that were inhibited by cAMP. Parallel studies that measured regulation of sodium permeability in fibroblasts showed similar results. In CF airway epithelia, the absence of this second function of CFTR as a cAMP-dependent regulator likely accounts for abnormal sodium transport.
囊性纤维化跨膜调节因子（CFTR）是在囊性纤维化（CF）患者中发生突变的基因产物，其作为环磷酸腺苷（cAMP）调节的氯离子通道具有公认的功能，但这一特性并不能解释CF气道上皮细胞中钠离子吸收的基础速率异常高以及对cAMP敏感性的问题。单独在Madin Darby犬肾（MDCK）上皮细胞中表达大鼠上皮钠离子通道（rENaC）的互补DNA会产生对氨氯地平敏感的大钠电流，该电流受到cAMP的刺激，而人CFTR与rENaC共表达则产生较小的基础钠电流，且该电流受到cAMP的抑制。测量成纤维细胞中钠通透性调节的平行研究显示了类似的结果。在CF气道上皮细胞中，CFTR作为cAMP依赖性调节因子的这第二种功能的缺失可能是钠转运异常的原因。
