Volume 31, No 7, Jul 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 7, July 2021: 758-772   |  Open Access

ORIGINAL ARTICLES

Direct control of store-operated calcium channels by ultrafast laser

Pan Cheng¹ , Xiaoying Tian¹ , Wanyi Tang¹ , Juan Cheng^2,3 , Jin Bao² , Haipeng Wang¹ , Sisi Zheng⁴ , Youjun Wang⁴ , Xunbin Wei¹ , Tunan Chen⁵ , Hua Feng⁵ , Tian Xue² , Keisuke Goda^6,7,8 , Hao He^1,*

¹School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
²School of life science, the University of Science and Technology of China, Hefei, Anhui 230026, China
³Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China
⁴Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China
⁵Institute of Neurosurgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China
⁶Department of Chemistry, University of Tokyo, Tokyo 113-0033, Japan
⁷Institute of Technological Sciences, Wuhan University, Wuhan, Hubei 430072, China
⁸Department of Bioengineering, University of California, Los Angeles, CA 90095, USA
These authors contributed equally: Pan Cheng, Xiaoying Tian. Correspondence: Hao He(haohe@sjtu.edu.cn)

Ca2+ channels are essential to cell birth, life, and death. They can be externally activated by optogenetic tools, but this requires robust introduction of exogenous optogenetic genes for expression of photosensitive proteins in biological systems. Here we present femtoSOC, a method for direct control of Ca2+ channels solely by ultrafast laser without the need for optogenetic tools or any other exogenous reagents. Specifically, by focusing and scanning wavelength-tuned low-power femtosecond laser pulses on the plasma membrane for multiphoton excitation, we directly induced Ca2+ influx in cultured cells. Mechanistic study reveals that photoexcited flavins covalently bind cysteine residues in Orai1 via thioether bonds, which facilitates Orai1 polymerization to form store-operated calcium channels (SOCs) independently of STIM1, a protein generally participating in SOC formation, enabling all-optical activation of Ca2+ influx and downstream signaling pathways. Moreover, we used femtoSOC to demonstrate direct neural activation both in brain slices in vitro and in intact brains of living mice in vivo in a spatiotemporal-specific manner, indicating potential utility of femtoSOC.

https://doi.org/10.1038/s41422-020-00463-9

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