TREK-1, a K+ channel involved in polymodal pain perception
TREK-1, a K+ channel involved in polymodal pain perception
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DOI：
10.1038/sj.emboj.7601116
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发表时间：
2006-06-07
期刊：
影响因子：
11.4
通讯作者：
Lazdunski, Michel
中科院分区：
文献类型：
--
作者：
Alloui, Abdelkrim;Zimmermann, Katharina;Lazdunski, Michel
TREK-1通道是一种温度敏感性、温度敏感性和机械门控性K+通道，受Gs和Gq偶联受体调节。这篇论文证明了TREK-1是参与疼痛感知的分子传感器之一。TREK-1在小感觉神经元中高度表达，存在于肽能和非肽能神经元中，并且与辣椒素激活的非选择性离子通道TRPV 1广泛共定位。TREK-1基因被破坏的小鼠对接近缺氧温暖和疼痛热之间的阈值的疼痛热感觉更敏感。这种表型与初级感觉神经元相关，因为在单纤维实验中发现多模态C纤维对热更敏感。敲除动物对低阈值机械刺激更敏感，并且在炎症条件下显示出增加的热和机械痛觉过敏。它们显示由渗透压变化引起的疼痛反应大大降低，特别是在前列腺素E2致敏的动物中。TREK-1是一种重要的多模式疼痛感知离子通道，也是开发新型镇痛药的一个有吸引力的靶点。
The TREK-1 channel is a temperature-sensitive, osmosensitive and mechano-gated K+ channel with a regulation by Gs and Gq coupled receptors. This paper demonstrates that TREK-1 qualifies as one of the molecular sensors involved in pain perception. TREK-1 is highly expressed in small sensory neurons, is present in both peptidergic and non-peptidergic neurons and is extensively colocalized with TRPV1, the capsaicin-activated nonselective ion channel. Mice with a disrupted TREK-1 gene are more sensitive to painful heat sensations near the threshold between anoxious warmth and painful heat. This phenotype is associated with the primary sensory neuron, as polymodal C-fibers were found to be more sensitive to heat in single fiber experiments. Knockout animals are more sensitive to low threshold mechanical stimuli and display an increased thermal and mechanical hyperalgesia in conditions of inflammation. They display a largely decreased pain response induced by osmotic changes particularly in prostaglandin E2-sensitized animals. TREK-1 appears as an important ion channel for polymodal pain perception and as an attractive target for the development of new analgesics.