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士鋒生物鈉離子通道電壓傳感器的性質(zhì)
最近更新時(shí)間：2014-2-8
提 供 商：上海士鋒生物科技有限公司資料大小：50.6KB
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神經(jīng)和肌肉細(xì)胞中的鈉離子通道隨跨膜電壓的變化而開(kāi)關(guān)。它們是產(chǎn)生神經(jīng)脈沖的關(guān)鍵，是很多毒素和藥物的作用目標(biāo)。與由電壓門(mén)控的鉀離子通道（由四個(gè)含有相同電壓傳感區(qū)域的亞單元組成）不同的是，鈉離子通道來(lái)自一個(gè)基因，含有四個(gè)不相同的電壓傳感區(qū)域。Bosmans等人利用對(duì)稱(chēng)鉀離子通道作為“記者”，來(lái)揭示移植進(jìn)一個(gè)鉀離子通道核中的各種不同鈉離子通道電壓傳感器的性質(zhì)。他們發(fā)現(xiàn)，“槳狀”區(qū)域?qū)︹c離子通道的功能很重要，毒素-“槳狀”區(qū)域互動(dòng)具有高度特異性。
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.