Potassium channels and the atomic basis of selective ion conduction
Potassium channels and the atomic basis of selective ion conduction
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DOI：
10.1007/s10540-004-7190-2
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发表时间：
2004-04-01
影响因子：
4
通讯作者：
MacKinnon, R
中科院分区：
文献类型：
--
作者：
MacKinnon, R
所有的活细胞都被一层薄的，大约40埃厚的脂双层所包围，称为细胞膜。细胞膜将细胞的内容物保持在一个地方，以便生命的化学反应可以发生，但它是某些基本成分（包括Na+，K+，Ca 2+和Cl）运动的障碍。对离子流过膜的屏障-称为介电屏障-可以在直观的水平上理解：细胞膜的内部包含油性物质，离子在水中比在油中更稳定。离子对水的能量偏好来自离子周围的电场及其与相邻分子的相互作用。水是一种可电极化的物质，这意味着它的分子在离子的电场中重新排列，使得负氧原子指向阳离子的方向，正氢原子指向阴离子。这些电稳定的相互作用在诸如油的较不极化的物质中要弱得多。因此，离子将倾向于停留在细胞膜两侧的水中，而不是进入和穿过膜。然而，许多细胞过程，从跨上皮细胞的电解质运输到神经元中的电信号产生，都依赖于跨膜的离子流动。细胞膜中存在一种称为离子通道的特殊蛋白质催化剂来调节这种流动。离子通道表现出以下三个基本特性：（1）它们快速传导离子;（2）许多离子通道具有高度选择性，这意味着只有某些离子种类流动，而其他离子被排除在外;（3）它们的功能受到称为门控的过程的调节，即离子传导响应于特定的环境刺激而打开和关闭。图1总结了这些特性。离子通道的现代历史始于1952年，当时Hodgkin和Huxley发表了关于鱿鱼巨轴突中动作电位理论的开创性论文[1-4]。他们理论的一个基本要素是轴突膜对Na+和K+离子的渗透性发生变化。Hodgkin-Huxley理论并没有说明细胞膜通透性变化的机制，
All living cells are surrounded by a thin, approximately 40 Athick lipid bilayer called the cell membrane. The cell membrane holds the contents of a cell in one place so that the chemistry of life can occur, but it is a barrier to the movement of certain essential ingredients including the ions Na+, K+, Ca2+, and Cl). The barrier to ion flow across the membrane—known as the dielectric barrier—can be understood at an intuitive level: the interior of the cell membrane comprises an oily substance and ions are more stable in water than in oil. The energetic preference of an ion for water arises from the electric field around the ion and its interaction with neighboring molecules. Water is an electrically polarizable substance, which means that its molecules rearrange in an ion’s electric field so that negative oxygen atoms point in the direction of cations and positive hydrogen atoms point toward anions. These electrically stabilizing interactions are much weaker in a less polarizable substance such as oil. Thus, an ion will tend to stay in the water on either side of a cell membrane rather than enter and cross the membrane. Yet numerous cellular processes, ranging from electrolyte transport across epithelia to electrical signal production in neurons, depend on the flow of ions across the membrane. To mediate the flow, specific protein catalysts known as ion channels exist in the cell membrane. Ion channels exhibit the following three essential properties:(1) they conduct ions rapidly;(2) many ion channels are highly selective, which means only certain ion species flow while others are excluded;(3) their function is regulated by processes known as gating, that is, ion conduction is turned on and off in response to specific environmental stimuli. Fig. 1 summarizes these properties. The modern history of ion channels began in 1952 when Hodgkin and Huxley published their seminal papers on the theory of the action potential in the squid giant axon [1–4]. A fundamental element of their theory was that the axon membrane undergoes changes in its permeability to Na+ and K+ ions. The Hodgkin–Huxley theory did not address the mechanism by which changes in the membrane perme-