通过多不和脂肪酸激活hTREK-1,需要直接相互作用
Emilie Bechard1, Elodie Arel1, Jamie Bride1
1PhyMedExp, Université de Montpellier, Inserm U1046, UMR CNRS 9412, CHU Arnaud de Villeneuve, Bâtiment Craste de Paulet, 370 Avenue du Doyen Gaston Giraud, 34290, Montpellier Cedex 05, France.
Scientific reports
|July 2, 2024
概括
多不和脂肪酸 (PUFA) 激活TREK-1通道,但不是通过膜张力变化. 它们的激活机制包括在膜插入后与通道的直接相互作用.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 离子通道生理学 离子通道生理学
背景情况:
- TREK-1是一种机械敏感的离子通道.
- 多不和脂肪酸 (PUFA) 是已知的TREK-1激活剂.
- 假设PUFA激活涉及膜张力变化.
研究的目的:
- 为了研究PUFA激活TREK-1的机制.
- 要将PUFA激活与已知的激活剂进行比较,ML402.
- 为了确定膜性质是否影响PUFA激活.
主要方法:
- 补丁电生理学 (全细胞和内外配置).
- 测量膜流动性的测量.
- 频谱转移分析以确定结合亲和力.
主要成果:
- 通过PUFA激活TREK-1是不同的,并且与构成性通道活性相关.
- 没有发现激活和脂肪酸链长度或双键数之间的相关性.
- 膜流动性在10μM时不受PUFA的影响.
- 对C22:6 n-3的结合亲和力 (KD,TREK1) 是44μM.
- PUFA和ML402显示出类似的激活动态和可逆性.
- PUFA从膜的两侧激活了TREK-1.从膜的两侧激活了TREK-1.
结论:
- 双层对假设并不能完全解释PUFA对TREK-1的激活.
- PUFA激活涉及两个步骤的机制:膜插入,然后是直接通道相互作用.
- PUFA的TREK-1结合部位可以从细胞内和细胞外两侧访问.
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