Na+ channel pharmacology and molecular mechanisms of gating.
Na+ channel pharmacology and molecular mechanisms of gating.
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Na通道药理学和门控分子机制。
DOI：
10.2174/138161206775474468
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发表时间：
2006
影响因子：
3.1
通讯作者：
I. Seyama
中科院分区：
文献类型：
--
作者：
K. Yamaoka;S. Vogel;I. Seyama
有效传播的动作电位的电发生需要同步开放跨膜Na+通道，该通道具有钠选择性过滤器、高通量离子电导途径和电压依赖性门控功能。Na+通道的这些特性长期以来一直是分子分析的目标。已知选择性结合Na+通道的几种毒素和药物已被用作药理学工具来研究Na+通道的电生理学或化学性质。最近对细菌电压依赖性K+通道的蛋白质晶体结构的分析为通道门控中涉及的移动的结构的识别提供了重要线索。新的信息可能适用于钠离子通道，并可能需要我们的理解钠通道的门控机制的全面修订。几个实验挑战了新兴的观点，即S6跨膜片段的通道门控是由膜脂质中漂浮的电压传感器的信号触发的。在此，我们回顾了各种毒素和药物分子，影响门控行为的Na+通道在这个新的结构框架，通过表征这些毒素的结合位点，并评估的药理作用所产生的毒素或钠通道的结构变化。
Electrogenesis of efficiently propagated action potentials requires synchronized opening of transmembrane Na+ channels possessing a sodium selectivity-filter, a high-throughput ion-conductance pathway, and voltage-dependent gating functions. These properties of the Na+ channel have long been the target of molecular analysis. Several toxins and drugs, known to selectively bind to Na+ channels, have been used as pharmacological tools to investigate Na+ channel properties either electrophysiologically or chemically. Recent analyses of the protein crystal structure of bacterial voltage-dependent K+ channels have provided important clues to the identity of mobile structures involved in channel gating. The new information may be applicable to Na+ channels, and may well require a total revision of our understanding of gating mechanisms of sodium channels. Several experiments challenge the emerging view that channel gating by S6 transmembrane segments is triggered by signals from voltage sensors floating in membrane lipid. Herein, we review the various toxin and drug molecules that affect the gating behavior of Na+ channels in this new structural framework, by characterizing the binding sites of these toxins, and assessing the pharmacological effects resulting from changes in the structure of the toxin or sodium channel.