Coupled ion movement underlies rectification in an inward-rectifier K+ channel.

Coupled ion movement underlies rectification in an inward-rectifier K+ channel.
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DOI:
10.1085/jgp.112.2.211
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发表时间:
1998-08
影响因子:
3.8
通讯作者:
Lu, Z
Lu, Z
中科院分区:
医学2区
文献类型:
--
作者:
Spassova, MA;Lu, Z

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我们研究了镁离子和五种季铵盐(四甲基铵、四乙基铵、四丙基铵、四丁基铵和四丁基铵)对ROMK1内向整流钾通道内孔的阻断作用。这些阻滞剂的表观亲和力随膜电压的变化而变化。因此,通道在内向比向外更有效地传导K+电流,即向内整流。虽然一些一价季铵盐的尺寸相当大,但在对称的100mMK+中,zδ值(测量它们与孔结合的电压依赖性)接近于1。此外,我们观察到,不仅阻滞剂本身的表观亲和力,而且它们对膜电压(或zδ)的依赖,都随着细胞外K+浓度的变化而变化。这些结果表明,阻滞性和渗透性(K+)离子的结合之间存在能量耦合,通道阻滞性的电压依赖性至少部分是K+离子在电场中运动的结果。进一步的定量分析解释了为什么内向整流的复杂现象既取决于膜电压又取决于K+的平衡电势。
We studied block of the internal pore of the ROMK1 inward-rectifier K+ channel by Mg2+ and five quaternary ammoniums (tetramethylammonium, tetraethylammonium, tetrapropylammonium, tetrabutylammonium, and tetrapentylammonium). The apparent affinity of these blockers varied as a function of membrane voltage. As a consequence, the channel conducted K+ current more efficiently in the inward than the outward direction; i.e., inward rectification. Although the size of some monovalent quaternary ammoniums is rather large, the zδ values (which measure voltage dependence of their binding to the pore) were near unity in symmetric 100 mM K+. Furthermore, we observed that not only the apparent affinities of the blockers themselves, but also their dependence on membrane voltage (or zδ), varied as a function of the concentration of extracellular K+. These results suggest that there is energetic coupling between the binding of blocking and permeating (K+) ions, and that the voltage dependence of channel blockade results, at least in part, from the movement of K+ ions in the electrical field. A further quantitative analysis of the results explains why the complex phenomenon of inward rectification depends on both membrane voltage and the equilibrium potential for K+.
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