双向TRP/L型Ca2+道/RyR/BKCa 血管光滑肌中的分子和功能信号复合
Dariia O Dryn1, Mariia I Melnyk1,2, Donal Melanaphy3
1O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 01024 Kyiv, Ukraine.
Biomolecules
|May 27, 2023
概括
血管光滑肌肉中的暂时受体潜能 (TRP) 通道介导复杂的收缩反应. 这项研究揭示了TRPV4和TRPM8通道激活了涉及BKCa和CaL通道的信号复合体,从而影响血管度.
科学领域:
- 生理学 生理学 生理学
- 药理学 药理学 是一个学科.
- 分子生物学分子生物学
背景情况:
- 暂时受体潜在 (TRP) 通道对于血管功能至关重要,但它们在血管组织中的机制尚未完全理解.
- TRP通道存在于血管肌细胞和内皮细胞中,影响细胞信号传递和收缩性.
研究的目的:
- 研究TRPV4通道在老鼠肺动脉收缩性中的作用.
- 阐明TRP通道介导的血管反应背后的分子机制.
- 为了比较TRPV4和TRPM8通道激活对血管光滑肌肉的影响.
主要方法:
- 使用了一种老鼠肺动脉模型与烯前收缩.
- 使用的TRPV4激动剂 (GSK1016790A) 和TRPM8激活剂 (孟托尔).
- 针对TRPV4 (HC067047),BKCa和L型电压门式Ca2+ (CaL) 通道使用选择性阻塞剂.
主要成果:
- TRPV4激活诱导了两相反应:最初放松,然后收缩.
- 放松是由BKCa激活和STOCs介导的;收缩是由TRPV4介导的脱极化激活CaL引起的.
- TRPV4和TRPM8的激活都导致了类似的膜电位变化,包括脱极化和STOCs.
结论:
- TRPV4通道在血管肌细胞中发挥着特定的作用,调解放松和收缩.
- 一个双向TRP-CaL-RyR-BKCa信号综合体被建议用于血管光滑肌.
- TRP通道通过与BKCa和CaL通道相互作用来调节本地和全球的Ca2+信号.
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