INVESTIGATION OF AN ALTERNATE CHLORIDE CONDUCTANCE IN CF

囊性纤维化是一种最终致命的疾病，涉及多个器官系统，包括呼吸道和胃肠道。它还影响生殖功能。患者往往死于进行性肺病，包括复发性感染和阻塞。其病理生理学的核心是离子转运的缺陷。具体而言，存在涉及囊性纤维化跨膜传导调节因子（CFTR）的缺陷，其导致跨上皮细胞的氯离子（Cl-）传导降低。有可能Cl-传导的替代途径可以绕过CFTR介导的缺陷。一个有希望的候选者，CLC-3，实际上可能是钙依赖性Cl-通道。有证据表明CFTR调节CLC-3。通过在转染细胞系和含有内源性CFTR和CLC-3的细胞系中进行膜片钳研究，可以阐明它们之间的关系。互补研究将包括反义、诱变和检查蛋白质-蛋白质和结构域-结构域相互作用的实验。

Cystic Fibrosis is an ultimately fatal disease which involves multiple organ systems including the respiratory and gastrointestinal tracts. It also affects reproductive function. Patients tend to die from progressive lung disease which involves recurrent infections and obstruction. Central to its pathophysiology is a defect in ion transport. Specifically, there is a defect involving the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) which results in decreased chloride (Cl-) conductance across epithelia. It is possible that an alternate pathway for Cl- conductance may bypass the CFTR mediated defect. A promising candidate, CLC-3, may in fact, be the calcium dependent Cl- channel. There is evidence that CFTR regulates CLC-3. It may be possible to elucidate their relationship to each other via patch-clamp studies in transfected cell lines and in cell lines containing endogenous CFTR and CLC-3. Complimentary studies would involve antisense, mutagenesis and experiments examining protein-protein and domain-domain interactions.