内皮TRPV4/Cx43信号综合体调节阻力动脉中的血管运动音调
Pía C Burboa1, Pablo S Gaete2, Ping Shu1
1Department of Pharmacology, Physiology and Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ 07103, U.S.A.
bioRxiv : the preprint server for biology
|August 2, 2024
概括
TRPV4通道的激活通过S-化,通过S-化在内皮细胞中打开连xin 43 (Cx43) 半通道,影响水平和调节血管度.
科学领域:
- 心血管生理学心血管生理学
- 内皮细胞生物学 内皮细胞生物学
- 离子通道功能的功能
背景情况:
- 连素43 (Cx43) 间隙结的S-基化影响细胞通信和半通道的开放.
- 内皮TRPV4通道通过氧化 (NO) 生产促进血管扩张.
- 在血管运动调节中Cx43半通道的确切作用尚未完全理解.
研究的目的:
- 通过TRPV4通道激活来研究内皮Cx43半通道的直接调制.
- 阐明TRPV4/Cx43信号通路在内皮电行为和血管运动调的作用.
主要方法:
- 近距离结合试验检测阻力动脉内皮中的Cx43和TRPV4近距离.
- 在初级内皮细胞培养 (ECs) 和ex vivo介质动脉中进行实验.
- 肠道显微镜 in vivo 评估TRPV4诱导的放松.
主要成果:
- 在EC中TRPV4的激活增强了eNOS活动,增加了NO的产生,并通过S-化开启了Cx43半通道.
- 阻断Cx43半通道可以降低TRPV4激活引起的细胞内Ca2+水平升高.
- 抑制Cx43半通道损害了内皮高极化,并在体内减弱了TRPV4诱导的放松.
结论:
- 通过S-化,TRPV4通道的激活直接调节内皮Cx43半通道.
- TRPV4/Cx43信号通路对于调节内皮电行为和血管运动调度至关重要.
- Cx43半通道在TRPV4介导的血管扩张中发挥着关键作用.
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