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氨基酸βββ1-40激活了脑毛细血管内皮细胞中的Piezo1通道

Xin Rui Lim¹, Luc Willemse¹, Osama F Harraz¹

¹Department of Pharmacology, Larner College of Medicine, Vermont Center for Cardiovascular and Brain Health, University of Vermont, Burlington, Vermont.

Biophysical journal

|December 26, 2024

概括

胺β改变大脑毛细体内皮质细胞Piezo1通道,增加它们的活性. 这一发现可能揭示了Piezo1.

科学领域:

神经科学是一个神经科学.
血管生物学血管生物学
离子通道生理学离子通道生理学

背景情况:

粉样β (Aβ) 的积累是神经退行的一个标志.
虽然Aβ会收缩大脑动脉和动脉,但它对毛细血管和内皮细胞 (ECs) 的作用尚不清楚.
机械敏感离子通道Piezo1在脑毛细血管EC中表达.

研究的目的:

为了研究Aβ1-40对大脑毛细血管内皮埃索1内皮质功能的影响.
为了确定Aβ1−40是否会改变EC中的Piezo1活性.

主要方法:

在新分离的毛细血管EC上进行补丁电生理学.
评估单通道Piezo1活动.
基因删除了Piezo1.1,使得它成为人类的基因.
使用一种超氧化物脱酶/酶模拟剂.

主要成果:

Aβ1-40增加了Piezo1的开放概率和通道开放时间.
通过Piezo1删除或抗氧化剂治疗消除了Aβ1-40的影响.
Aβ1-40增强了Piezo1的机械敏感性,并降低了激活压力.
Aβ1-40促进了脑EC中Piezo1介导的阳离子流入的增加.

结论:

在脑毛细血管EC中,Aβ1-40调节Piezo1功能.
这种调制导致了阴离子流入的增加.
通过Aβ调节皮埃佐1,可能在神经退行性疾病的病理生理学中发挥作用.

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