A proton pore in a potassium channel voltage sensor reveals a focused electric field
A proton pore in a potassium channel voltage sensor reveals a focused electric field
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DOI：
10.1038/nature02270
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发表时间：
2004-02-05
期刊：
影响因子：
64.8
通讯作者：
Bezanilla, F
中科院分区：
文献类型：
--
作者：
Starace, DM;Bezanilla, F
电压依赖性钾通道对于神经冲动的产生至关重要（1）。电压敏感性由主要位于构成通道的四个相同亚基中的每一个的第四跨膜区段（S4）中的带电残基赋予。当跨膜的电位差改变时，这些带电片段重新定位（2，3），控制孔传导离子的能力。在Aeropyrum pernix钾通道KvAP（4）的晶体结构中，S4和部分第三（S3 B）跨膜α-螺旋通过称为“电压传感器桨”的排列中的发夹转角连接。这种结构被认为在通道激活期间穿过脂质双层，将正电荷运输穿过膜的大部分（5）。在这里，我们表明，取代第一个S4精氨酸组氨酸在振动钾通道创建一个质子孔时，细胞是超极化。这种孔的形成并不支持桨模型，因为质子将无法进入脂质掩埋的组氨酸。我们的结论是，在超极化电位，水和质子的内部和外部的解决方案必须分开的一个狭窄的障碍，在通道蛋白集中电场到一个小的电压敏感区域。
Voltage-dependent potassium channels are essential for the generation of nerve impulses(1). Voltage sensitivity is conferred by charged residues located mainly in the fourth transmembrane segment (S4) of each of the four identical subunits that make up the channel. These charged segments relocate when the potential difference across the membrane changes(2,3), controlling the ability of the pore to conduct ions. In the crystal structure of the Aeropyrum pernix potassium channel KvAP(4), the S4 and part of the third (S3B) transmembrane alpha-helices are connected by a hairpin turn in an arrangement termed the 'voltage-sensor paddle'. This structure was proposed to move through the lipid bilayer during channel activation, transporting positive charges across a large fraction of the membrane(5). Here we show that replacing the first S4 arginine by histidine in the Shaker potassium channel creates a proton pore when the cell is hyperpolarized. Formation of this pore does not support the paddle model, as protons would not have access to a lipid-buried histidine. We conclude that, at hyperpolarized potentials, water and protons from the internal and external solutions must be separated by a narrow barrier in the channel protein that focuses the electric field to a small voltage-sensitive region.