Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries.
Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries.
复制标题
压电1是中枢神经系统毛细血管中的机械传感器通道。
DOI：
10.1161/circresaha.122.320827
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发表时间：
2022-05-13
影响因子：
20.1
通讯作者：
Nelson, Mark T.
中科院分区：
文献类型：
--
作者：
Harraz, Osama F.;Klug, Nicholas R.;Senatore, Amanda J.;Hill-Eubanks, David C.;Nelson, Mark T.
关键词：
毛细血管能够感知释放到毛细血管外壁上的神经血管耦合剂，将这些外部信号转化为电/Ca2+变化，这在血流调节中发挥着至关重要的作用，并确保满足神经元的需求。然而，由于施加到管腔上的力而产生的控制机制尚不清楚。在这里，我们展示了 Piezo1 通道在中枢神经系统 (CNS) 毛细血管中充当机械传感器。电生理学分析证实了 Piezo1 通道在大脑皮质和视网膜毛细血管中的表达和功能。 Piezo1 通道的激活会引发对内皮细胞特异性 Piezo1 缺失敏感的电流。使用基因编码的 Ca2+ 指示小鼠和离体加压视网膜制剂，我们发现机械力激活 Piezo1 通道会触发毛细血管内皮细胞中的 Ca2+ 信号。总的来说，这些发现表明 Piezo1 通道是毛细管机械传感器，可以启动关键的 Ca2+ 信号，因此可能对 CNS 血流控制产生深远的影响。毛细血管能够感知神经血管耦合剂，这些耦合剂在血流调节和确保满足神经元需求方面发挥着至关重要的作用。然而，调节施加到管腔上的力的控制机制尚不清楚。这项研究提供了 Piezo1 通道在中枢神经系统毛细血管中表达并发挥功能的证据。血管腔内机械力激活 Piezo1 通道会触发内皮钙信号。
Capillaries are equipped to sense neurovascular coupling agents released onto the outer wall of a capillary, translating these external signals into electrical/Ca2+ changes that play a crucial role in blood flow regulation and ensuring that neuronal demands are met. However, control mechanisms attributable to forces imposed onto the lumen are less clear. Here, we show that Piezo1 channels act as mechanosensors in central nervous system (CNS) capillaries. Electrophysiological analyses confirmed expression and function of Piezo1 channels in brain cortical and retinal capillaries. Activation of Piezo1 channels evoked currents that were sensitive to endothelial cell-specific Piezo1 deletion. Using genetically encoded Ca2+ indicator mice and an ex vivo pressurized retina preparation, we found that activation of Piezo1 channels by mechanical forces triggered Ca2+ signals in capillary endothelial cells. Collectively, these findings indicate that Piezo1 channels are capillary mechanosensors that initiate crucial Ca2+ signals and could therefore have a profound impact on CNS blood flow control. Capillaries are equipped to sense neurovascular coupling agents that play a crucial role in blood flow regulation and ensuring that neuronal demands are met. However, control mechanisms that regulate the forces imposed onto the lumen have been unclear. This study provides evidence that Piezo1 channel is expressed and functional in CNS capillaries. The activation of Piezo1 channel by mechanical forces in the vascular lumen triggers endothelial calcium signals.