Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K+ Channel 1). A Novel Therapeutic Target?
Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K+ Channel 1). A Novel Therapeutic Target?
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DOI：
10.1021/acs.jmedchem.5b00671
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发表时间：
2016-06-09
影响因子：
7.3
通讯作者：
Ducki, Sylvie
中科院分区：
文献类型：
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作者：
Vivier, Delphine;Bennis, Khalil;Ducki, Sylvie
钾 (K+) 通道是在大多数活细胞中表达的膜蛋白，可选择性控制 K+ 离子的流动。人类基因组中有超过 80 个基因编码 K+ 通道亚基。 TVVIK 相关 K+ 通道 (TREK-1) 属于双孔域 K+ 通道 (K2P)，并表现出各种特性，包括对物理刺激（膜拉伸、酸中毒、温度）和化学刺激（信号脂质、挥发性麻醉剂）的敏感性。 TREK-1 在中枢神经系统中的分布，加上其打开和关闭的生理后果，导致该通道成为有吸引力的治疗靶点。我们回顾了 TREK-1 通道、其结构和功能特性以及能够调节其门控的药理学制剂（激动剂和拮抗剂）。
Potassium (K+) channels are membrane proteins expressed in most living cells that selectively control the flow of K+ ions. More than 80 genes encode the K+ channel subunits in the human genome. The TVVIK-related K+ channel(TREK-1) belongs to the two-pore domain K+ channels (K2P) and displays various properties including sensitivity to physical (membrane stretch, acidosis, temperature) and chemical stimuli (signaling lipids, volatile anesthetics). The distribution of TREK-1 in the central nervous system, coupled with the physiological consequences of its opening and closing, leads to the emergence of this channel as an attractive therapeutic target. We review the TREK-1 channel, its structural and functional properties, and the pharmacological agents (agonists and antagonists) able to modulate its gating.