TREK-1, a K+ channel involved in neuroprotection and general anesthesia
TREK-1, a K+ channel involved in neuroprotection and general anesthesia
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DOI：
10.1038/sj.emboj.7600234
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发表时间：
2004-07-07
期刊：
影响因子：
11.4
通讯作者：
Lazdunski, M
中科院分区：
文献类型：
--
作者：
Heurteaux, C;Guy, N;Lazdunski, M
TREK-1是一个在整个中枢神经系统表达的双孔结构域背景钾通道。它由多不饱和脂肪酸和溶血磷脂打开。它被产生细胞内cAMP增加的神经递质和激活Gq蛋白通路的神经递质所抑制。TREK-1也被挥发性麻醉药激活，并被认为是这些药物作用的重要靶点。利用TREK-1基因被破坏的小鼠，我们现在发现TREK-1在抗癫痫和脑和脊髓缺血的神经保护中具有重要作用。Trek1（-/-）小鼠对缺血和癫痫的敏感性增加。多不饱和脂肪酸的神经保护作用，在Trek1（+/+）小鼠中令人印象深刻，在Trek1（-/-）小鼠中消失，表明TREK-1在这一过程中起核心作用。Trek1（-/-）小鼠对挥发性麻醉药也有耐药性。TREK-1成为开发神经和麻醉学新治疗剂的潜在创新靶点。
TREK-1 is a two-pore-domain background potassium channel expressed throughout the central nervous system. It is opened by polyunsaturated fatty acids and lysophospholipids. It is inhibited by neurotransmitters that produce an increase in intracellular cAMP and by those that activate the Gq protein pathway. TREK-1 is also activated by volatile anesthetics and has been suggested to be an important target in the action of these drugs. Using mice with a disrupted TREK-1 gene, we now show that TREK-1 has an important role in neuroprotection against epilepsy and brain and spinal chord ischemia. Trek1(-/-) mice display an increased sensitivity to ischemia and epilepsy. Neuroprotection by polyunsaturated fatty acids, which is impressive in Trek1(+/+) mice, disappears in Trek1(-/-) mice indicating a central role of TREK-1 in this process. Trek1(-/-) mice are also resistant to anesthesia by volatile anesthetics. TREK-1 emerges as a potential innovative target for developing new therapeutic agents for neurology and anesthesiology.