An ion's view of the potassium channel. The structure of the permeation pathway as sensed by a variety of blocking ions.
An ion's view of the potassium channel. The structure of the permeation pathway as sensed by a variety of blocking ions.
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DOI：
10.1085/jgp.85.5.669
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发表时间：
1985-05
期刊：
影响因子：
--
通讯作者：
Shoukimas JJ
中科院分区：
文献类型：
--
作者：
French RJ;Shoukimas JJ
我们研究了9种有机阳离子和碱阳离子对电压夹紧的鱿鱼巨轴突钾离子通道的阻断作用，以了解钾离子通道如何选择进入的离子。当加入到内部溶液中时，所有的离子都阻塞了通道，内部正电压增强了阻塞。铯也从外部阻断了通道，而内部负电压有利于阻断。我们通过估计到阻塞点的“视电距离”来比较不同离子进入通道的深度。三势垒双占用模型的模拟表明，如果阻断离子能够完全通过通道，则“表观电距离”（表示为总跨膜电压的一小部分）似乎小于实际值。这些计算加强了我们的结论，即钠和铯比锂和有机阻滞剂占据的位置更深入通道。我们的结果，连同早期的工作一起考虑，表明离子可以轻易渗透到钾通道的深度取决于其大小和其分子表面的特定化学基团。在季铵离子的烷基链上添加羟基，既可以降低结合强度，又可以使其更深入地渗透到通道中。对于碱阳离子来说，水合程度可能是决定离子能穿透多远的关键。水合程度最高的锂似乎没有钠和铯渗透得那么深。我们的数据表明，钾离子通道的渗透途径中至少有四个离子结合位点，同时至少占用两个。
We have studied the block of potassium channels in voltage-clamped squid giant axons by nine organic and alkali cations, in order to learn how the channel selects among entering ions. When added to the internal solution, all of the ions blocked the channels, with inside-positive voltages enhancing the block. Cesium blocked the channels from the outside as well, with inside-negative voltages favoring block. We compared the depths to which different ions entered the channel by estimating the "apparent electrical distance" to the blocking site. Simulations with a three-barrier, double-occupancy model showed that the "apparent electrical distance," expressed as a fraction of the total transmembrane voltage, appears to be less than the actual value if the blocking ion can pass completely through the channel. These calculations strengthen our conclusion that sodium and cesium block at sites further into the channel than those occupied by lithium and the organic blockers. Our results, considered together with earlier work, demonstrate that the depth to which an ion can readily penetrate into the potassium channel depends both on its size and on the specific chemical groups on its molecular surface. The addition of hydroxyl groups to alkyl chains on a quaternary ammonium ion can both decrease the strength of binding and allow deeper penetration into the channel. For alkali cations, the degree of hydration is probably crucial in determining how far an ion penetrates. Lithium, the most strongly hydrated, appeared not to penetrate as far as sodium and cesium. Our data suggest that there are, minimally, four ion binding sites in the permeation pathway of the potassium channel, with simultaneous occupancy of at least two.