Molecular dissection of gating in the CIC-2 chloride channel
Molecular dissection of gating in the CIC-2 chloride channel
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DOI：
10.1093/emboj/16.7.1582
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发表时间：
1997-04-01
期刊：
影响因子：
11.4
通讯作者：
Jentsch, TJ
中科院分区：
文献类型：
--
作者：
Jordt, SE;Jentsch, TJ
CIC - 2氯离子通道可能参与细胞体积和神经元兴奋性的调节。定点突变被用于了解CIC - 2在响应细胞肿胀、超极化和酸性细胞外pH时的激活情况。与CIC - 0中的等效突变类似，中和跨膜结构域末端的Lys566会导致外向整流以及电压依赖性的改变，但基本的门控机制（包括肿胀激活）保持完整。相反，跨膜结构域D7和D8之间的细胞质环中的突变通过持续打开通道而不改变其孔道特性，消除了所有三种激活模式。这些效应类似于缺失氨基末端失活结构域时所观察到的效应，并表明它可能作为其受体发挥作用。这种“球 - 链”型机制可能作为由多种刺激引发的CIC - 2激活的最终途径。
The CIC-2 chloride channel is probably involved in the regulation of cell volume and of neuronal excitability. Site-directed mutagenesis was used to understand CIC-2 activation in response to cell swelling, hyperpolarization and acidic extracellular pH. Similar to equivalent mutations in CIC-0, neutralizing Lys566 at the end of the transmembrane domains results in outward rectification and a shift in voltage dependence, but leaves the basic gating mechanism, including swelling activation, intact. In contrast, mutations in the cytoplasmic loop between transmembrane domains D7 and D8 abolish all three modes of activation by constitutively opening the channel without changing its pore properties. These effects resemble those observed with deletions of an amino-terminal inactivation domain, and suggest that it may acta as its receptor. Such a 'ball-and-chain' type mechanism may act as a final pathway in the activation of CIC-2 elicited by several stimuli.