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首页> 外文期刊>American Journal of Physiology >Voltage-sensitive gating induced by a mutation in the fifth transmembrane domain of CFTR.
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Voltage-sensitive gating induced by a mutation in the fifth transmembrane domain of CFTR.

机译：CFTR的第五个跨膜结构域中的突变引起的电压敏感门控。

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摘要

A mutation in the fifth transmembrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel (V317E) resulted in whole cell currents that exhibited marked outward rectification on expression in Xenopus oocytes. However, the single-channel unitary current (i)-voltage (V) relationship failed to account for the rectification of whole cell currents. In excised patches containing one to a few channels, the time-averaged single-channel current (I)-V relationship (I = N x P(o) x i, where N is the number of active channels and P(o) is open probability) of V317E CFTR displayed outward rectification, whereas that of wild-type CFTR was linear, indicating that the P(o) of V317E CFTR is voltage dependent. The decrease in P(o) at negative potentials was due to both a decreased burst duration and a decreased opening rate that could not be ameliorated by a 10-fold increase in ATP concentration. This behavior appears to reflect a true voltage dependence of the gating process because the P(o)-V relationship did not depend on the direction of Cl(-) movement. The results are consistent with the introduction, by a point mutation, of a novel voltage-dependent gating mode that may provide a useful tool for probing the portions of the protein that move in response to ATP-dependent gating.
机译：囊性纤维化跨膜电导调节剂（CFTR）Cl（-）通道（V317E）的第五个跨膜结构域中的突变导致全细胞电流在非洲爪蟾卵母细胞中表达时表现出明显的向外整流。但是，单通道unit电流（i）-电压（V）的关系无法解决整个电池电流的整流问题。在包含一个或几个通道的已切除补丁中，时间平均单通道电流（I）-V关系（I = N x P（o）xi，其中N为活动通道数，P（o）为开路V317E CFTR的概率显示为向外整流，而野生型CFTR的则为线性，表明V317E CFTR的P（o）与电压有关。负电位下P（o）的降低是由于猝发持续时间的减少和开孔率的降低，而这不能通过ATP浓度增加10倍来改善。此行为似乎反映了门控过程的真实电压依赖性，因为P（o）-V关系不取决于Cl（-）移动的方向。结果与通过点突变引入新的电压依赖性门控模式相一致，该新颖的电压依赖性门控模式可为探测响应于ATP依赖性门控而移动的蛋白质部分提供有用的工具。

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