A MULTIFUNCTIONAL AQUEOUS CHANNEL FORMED BY CFTR

A MULTIFUNCTIONAL AQUEOUS CHANNEL FORMED BY CFTR
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DOI:
10.1126/science.1279809
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发表时间:
1992-11-27
期刊:
影响因子:
56.9
通讯作者:
VERKMAN, AS
VERKMAN, AS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HASEGAWA, H;SKACH, W;VERKMAN, AS

文献摘要

被引文献

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囊性纤维化基因产物(CFTR)是一种复杂的蛋白质,其功能是作为腺苷3,5-一磷酸(CAMP)刺激的离子通道,并可能作为细胞内过程的调节器。为了确定CFTR分子是否包含一个功能性的水通道,我们对表达CFTR的非洲爪哇卵母细胞的阴离子、水和尿素的转运进行了测量。环状AMP激动剂可诱导94微米的氯离子电导和4×10(-4)厘米/秒的水通透性增加,这种增加可被氯离子通道阻滞剂抑制,并依赖于阴离子组成。CFTR计算的单通道水导为每秒9x10(-13)立方厘米,表明存在孔状水路。表达CFTR的卵母细胞也表现出cAMP刺激的尿素转运,但不显示较大的溶质蔗糖。因此,CFTR包含一个cAMP刺激的水孔,可以运输阴离子、水和小溶质。这些结果也为水通过离子通道的运动提供了功能证据。
The cystic fibrosis gene product (CFTR) is a complex protein that functions as an adenosine 3,5-monophosphate (cAMP)-stimulated ion channel and possibly as a regulator of intracellular processes. In order to determine whether the CFTR molecule contains a functional aqueous pathway, anion, water, and urea transport were measured in Xenopus oocytes expressing CFTR. Cyclic AMP agonists induced a Cl- conductance of 94 microsiemens and an increase in water permeability of 4 x 10(-4) centimeter per second that was inhibited by a Cl- channel blocker and was dependent on anion composition. CFTR has a calculated single channel water conductance of 9 x 10(-13) cubic centimeter per second, suggesting a pore-like aqueous pathway. Oocytes expressing CFTR also showed cAMP-stimulated transport of urea but not the larger solute sucrose. Thus CFTR contains a cAMP-stimulated aqueous pore that can transport anions, water, and small solutes. The results also provide functional evidence for water movement through an ion channel.