Valverde M A, O'Brien J A, Sepúlveda F V, Ratcliff R A, Evans M J, Colledge W H
Nuffield Department of Clinical Biochemistry, University of Oxford, John Radcliffe Hospital, United Kingdom.
Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9038-41. doi: 10.1073/pnas.92.20.9038.
Cystic fibrosis is a disease characterized by abnormalities in the epithelia of the lungs, intestine, salivary and sweat glands, liver, and reproductive systems, often as a result of inadequate hydration of their secretions. The primary defect in cystic fibrosis is the altered activity of a cAMP-activated Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) channel. However, it is not clear how a defect in the CFTR Cl- channel function leads to the observed pathological changes. Although much is known about the structural properties and regulation of the CFTR, little is known of its relationship to cellular functions other than the cAMP-dependent Cl- secretion. Here we report that cell volume regulation after hypotonic challenge is also defective in intestinal crypt epithelial cells isolated from CFTR -/- mutant mice. Moreover, the impairment of the regulatory volume decrease in CFTR -/- crypts appears to be related to the inability of a K+ conductance to provide a pathway for the exit of this cation during the volume adjustments. This provides evidence that the lack of CFTR protein may have additional consequences for the cellular function other than the abnormal cAMP-mediated Cl- secretion.
囊性纤维化是一种以肺、肠道、唾液腺、汗腺、肝脏和生殖系统上皮异常为特征的疾病，其分泌物水化不足常是导致该疾病的原因。囊性纤维化的主要缺陷是一种cAMP激活的氯离子通道——囊性纤维化跨膜传导调节因子（CFTR）通道的活性改变。然而，目前尚不清楚CFTR氯离子通道功能缺陷是如何导致所观察到的病理变化的。尽管人们对CFTR的结构特性和调节已有很多了解，但除了cAMP依赖的氯离子分泌外，对其与细胞功能的关系知之甚少。在此，我们报告从CFTR基因敲除突变小鼠分离的肠隐窝上皮细胞在低渗刺激后的细胞体积调节也存在缺陷。此外，CFTR基因敲除隐窝中调节性容积减小的损伤似乎与钾离子通道在容积调节过程中无法为该阳离子提供流出途径有关。这提供了证据，表明CFTR蛋白的缺失除了导致异常的cAMP介导的氯离子分泌外，可能对细胞功能还有其他影响。
