EVIDENCE THAT THE S6 SEGMENT OF THE SHAKER VOLTAGE-GATED K+ CHANNEL COMPRISES PART OF THE PORE

EVIDENCE THAT THE S6 SEGMENT OF THE SHAKER VOLTAGE-GATED K+ CHANNEL COMPRISES PART OF THE PORE
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DOI:
10.1038/367179a0
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发表时间:
1994-01-13
期刊:
影响因子:
64.8
通讯作者:
JAN, LY
JAN, LY
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LOPEZ, GA;JAN, YN;JAN, LY

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钾离子通道具有很高的选择性,允许钾离子快速通过它们的孔道。一些研究表明,H5(P或SS1-SS2)段2,3是电压门控离子通道4-10中孔的一部分。H5跨越至少80%的K+通道5,11的电势降是基于H5残基的突变引起的内部四乙基铵敏感性的改变,这些突变在对四乙基氨5-7,12,13具有不同敏感性的K+通道中是100%保守的。在这里,我们报告了S6片段也参与了K+离子的渗透,并调节了内部四乙基铵和钡的敏感性。将NGK2的S6片段移植到Shaker中,使这个S6嵌合体采用单通道电导,并对来自NGK2通道的内部四乙基铵和钡离子敏感。NGK2和Shaker在外部四乙基铵敏感性上的差异,而不是单通道电导的差异,可以归因于它们H5序列的差异。已发现三个非保守的S6残基影响单通道电导或内部四乙基铵敏感性。
POTASSIUM channels are highly selective and allow the rapid flux of potassium ions through their pore1. Several studies have implicated the H5 (P or SS1-SS2) segment2,3 as part of the pore in voltage-gated ion channels4-10. The proposal that H5 spans at least 80% of the electric potential drop across the K+ channel pore5,11 is based on altered internal tetraethylammonium sensitivity arising from mutations of H5 residues that are 100% conserved among K+ channels having differing sensitivity to tetraethylammonium5-7,12,13. Here we report that the S6 segment is also involved in K+ ion permeation and in governing the sensitivity to internal tetraethylammonium and barium. Transplanting the S6 segment of NGK2 into Shaker causes this S6 chimaera to adopt the single-channel conductance and sensitivity to internal tetraethylammonium and barium ions from the NGK2 channel. The differences between NGK2 and Shaker in external tetraethylammonium sensitivity, but not single-channel conductance, can be attributed to the differences in their H5 sequences. Three non-conserved S6 residues have been found to affect either single-channel conductance or internal tetraethylammonium sensitivity.