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Piezo1和Piezo2离子通道对重复性机械刺激的转导

Transduction of Repetitive Mechanical Stimuli by Piezo1 and Piezo2 Ion Channels.

作者信息

Lewis Amanda H, Cui Alisa F, McDonald Malcolm F, Grandl Jörg

机构信息

Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.

Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Cell Rep. 2017 Jun 20;19(12):2572-2585. doi: 10.1016/j.celrep.2017.05.079.

Abstract

Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations. We find that both channels function as pronounced frequency filters whose transduction efficiencies vary with stimulus frequency, waveform, and duration. We then use numerical simulations and human disease-related point mutations to demonstrate that channel inactivation is the molecular mechanism underlying frequency filtering and further show that frequency filtering is conserved in rapidly adapting mouse DRG neurons. Our results give insight into the potential contributions of Piezos in transducing repetitive mechanical stimuli.

摘要

几种细胞类型会经历重复性机械刺激,包括脉动血流期间的静脉内皮细胞、声音暴露时的内耳毛细胞,以及在粗糙表面上扫过或触摸振动物体时的皮肤细胞及其支配的背根神经节(DRG)神经元。虽然机械敏感的Piezo离子通道在感知静态触摸方面的作用已明确,但它们在转导重复性刺激中的作用尚不清楚。在这里,我们对异源表达的小鼠Piezo1和Piezo2响应重复性机械刺激进行了电生理记录。我们发现这两种通道都起着明显的频率滤波器作用,其转导效率随刺激频率、波形和持续时间而变化。然后我们使用数值模拟和与人类疾病相关的点突变来证明通道失活是频率滤波的分子机制,并进一步表明频率滤波在快速适应的小鼠DRG神经元中是保守的。我们的结果深入了解了Piezo通道在转导重复性机械刺激中的潜在作用。

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