Automated parallel recordings of topologically identified single ion channels.
Automated parallel recordings of topologically identified single ion channels.
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DOI：
10.1038/srep01995
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发表时间：
2013
影响因子：
4.6
通讯作者：
Takeuchi, Shoji
中科院分区：
文献类型：
--
作者：
Kawano, Ryuji;Tsuji, Yutaro;Sato, Koji;Osaki, Toshihisa;Kamiya, Koki;Hirano, Minako;Ide, Toru;Miki, Norihisa;Takeuchi, Shoji
尽管离子通道是药物发现的有吸引力的靶点，但系统地筛选离子通道靶向药物仍然具有挑战性。为了便于自动化的单离子通道记录与内和胞外结构域的药物相互作用的分析，我们已经开发了一种并行记录方法，使用人工细胞膜。在液滴室阵列中使用稳定的脂质双层形成促进了来自重构的天然和突变离子通道的自动化、平行、单通道记录。使用该系统，通过确定蛋白质方向来表征多种类型的离子通道，包括突变形式。此外，我们提供的证据表明，内和细胞外淀粉样β片段直接抑制hBK通道的通道开放概率。这种自动化的方法提供了一个高通量的药物筛选系统的离子通道的目标和数据密集型分析技术研究离子通道门控机制。
Although ion channels are attractive targets for drug discovery, the systematic screening of ion channel-targeted drugs remains challenging. To facilitate automated single ion-channel recordings for the analysis of drug interactions with the intra- and extracellular domain, we have developed a parallel recording methodology using artificial cell membranes. The use of stable lipid bilayer formation in droplet chamber arrays facilitated automated, parallel, single-channel recording from reconstituted native and mutated ion channels. Using this system, several types of ion channels, including mutated forms, were characterised by determining the protein orientation. In addition, we provide evidence that both intra- and extracellular amyloid-beta fragments directly inhibit the channel open probability of the hBK channel. This automated methodology provides a high-throughput drug screening system for the targeting of ion channels and a data-intensive analysis technique for studying ion channel gating mechanisms.
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影响因子：
--
作者：
Bayley H;Cronin B;Heron A;Holden MA;Hwang WL;Syeda R;Thompson J;Wallace M
通讯作者：
Wallace M
影响因子：
7.4
作者：
Le Pioufle, Bruno;Suzuki, Hiroaki;Takeuchi, Shoji
通讯作者：
Takeuchi, Shoji
影响因子：
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作者：
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通讯作者：
Duran, Randolph S.
影响因子：
15
作者：
Kawano, Ryuji;Osaki, Toshihisa;Takeuchi, Shoji
通讯作者：
Takeuchi, Shoji
影响因子：
3.4
作者：
Hirano, Minako;Onishi, Yukiko;Ide, Toru
通讯作者：
Ide, Toru