The Mechanosensitive Ion Channel Piezo1 Significantly Mediates In Vitro Ultrasonic Stimulation of Neurons

Zhihai Qiu; Jinghui Guo; Shashwati Kala; Jiejun Zhu; Quanxiang Xian; Weibao Qiu; Guofeng Li; Ting Zhu; Long Meng; Rui Zhang; Hsiao Chang Chan; Hairong Zheng; Lei Sun

doi:10.1016/j.isci.2019.10.037

The Mechanosensitive Ion Channel Piezo1 Significantly Mediates In Vitro Ultrasonic Stimulation of Neurons

iScience. 2019 Nov 22:21:448-457. doi: 10.1016/j.isci.2019.10.037. Epub 2019 Oct 23.

Authors

Zhihai Qiu¹, Jinghui Guo², Shashwati Kala¹, Jiejun Zhu¹, Quanxiang Xian¹, Weibao Qiu³, Guofeng Li³, Ting Zhu¹, Long Meng³, Rui Zhang¹, Hsiao Chang Chan⁴, Hairong Zheng⁵, Lei Sun⁶

Affiliations

¹ Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR 999077, P. R. China.
² Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR 999077, P. R. China; Department of Physiology, School of Medicine, Jinan University, Guangzhou, China.
³ Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P. R. China.
⁴ Department of Physiology, School of Medicine, Jinan University, Guangzhou, China.
⁵ Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P. R. China. Electronic address: hr.zheng@siat.ac.cn.
⁶ Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR 999077, P. R. China. Electronic address: lei.sun@polyu.edu.hk.

Abstract

Ultrasound brain stimulation is a promising modality for probing brain function and treating brain disease non-invasively and with high spatiotemporal resolution. However, the mechanism underlying its effects remains unclear. Here, we examine the role that the mouse piezo-type mechanosensitive ion channel component 1 (Piezo1) plays in mediating the in vitro effects of ultrasound in mouse primary cortical neurons and a neuronal cell line. We show that ultrasound alone could activate heterologous and endogenous Piezo1, initiating calcium influx and increased nuclear c-Fos expression in primary neurons but not when pre-treated with a Piezo1 inhibitor. We also found that ultrasound significantly increased the expression of the important proteins phospho-CaMKII, phospho-CREB, and c-Fos in a neuronal cell line, but Piezo1 knockdown significantly reduced this effect. Our findings demonstrate that the activity of mechanosensitive ion channels such as Piezo1 stimulated by ultrasound is an important contributor to its ability to stimulate cells in vitro.

Keywords: Cellular Neuroscience; Molecular Neuroscience; Neuroscience; Sensory Neuroscience.