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Nature:钠离子通道电压传感器的性质

来源:Nature 2008-11-18 10:33

专题:Nature报道

神经和肌肉细胞中的钠离子通道随跨膜电压的变化而开关。它们是产生神经脉冲的关键,是很多毒素和药物的作用目标。与由电压门控的钾离子通道(由四个含有相同电压传感区域的亚单元组成)不同的是,钠离子通道来自一个基因,含有四个不相同的电压传感区域。Bosmans等人利用对称钾离子通道作为“记者”,来揭示移植进一个钾离子通道核中的各种不同钠离子通道电压传感器的性质。他们发现,“桨状”区域对钠离子通道的功能很重要,毒素-“桨状”区域互动具有高度特异性。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature 456, 202-208 (13 November 2008) | doi:10.1038/nature07473

Deconstructing voltage sensor function and pharmacology in sodium channels

Frank Bosmans1,2, Marie-France Martin-Eauclaire3 & Kenton J. Swartz1

1 Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
2 Laboratory of Toxicology, University of Leuven, 3000 Leuven, Belgium
3 CNRS UMR 6231, CRN2M, Institut Jean Roche, Université de la Méditerranée, Marseille Cedex 20, France

Abstract

Voltage-activated sodium (Nav) channels are crucial for the generation and propagation of nerve impulses, and as such are widely targeted by toxins and drugs. The four voltage sensors in Nav channels have distinct amino acid sequences, raising fundamental questions about their relative contributions to the function and pharmacology of the channel. Here we use four-fold symmetric voltage-activated potassium (Kv) channels as reporters to examine the contributions of individual S3b–S4 paddle motifs within Nav channel voltage sensors to the kinetics of voltage sensor activation and to forming toxin receptors. Our results uncover binding sites for toxins from tarantula and scorpion venom on each of the four paddle motifs in Nav channels, and reveal how paddle-specific interactions can be used to reshape Nav channel activity. One paddle motif is unique in that it slows voltage sensor activation, and toxins selectively targeting this motif impede Nav channel inactivation. This reporter approach and the principles that emerge will be useful in developing new drugs for treating pain and Nav channelopathies.

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