Direct visualization of general anesthetic propofol on neurons by stimulated Raman scattering microscopy
Robert Oda,
Jingwen Shou,
Wenying Zhong,
Yasuyuki Ozeki,
Masato Yasui,
Mutsuo Nuriya
Affiliations
Robert Oda
Department of Pharmacology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan; Department of Electrical Engineering and Information Systems, Graduate School of Engineering, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan; Corresponding author
Jingwen Shou
Department of Electrical Engineering and Information Systems, Graduate School of Engineering, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan
Wenying Zhong
Department of Pharmacology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
Yasuyuki Ozeki
Department of Electrical Engineering and Information Systems, Graduate School of Engineering, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan
Masato Yasui
Department of Pharmacology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
Mutsuo Nuriya
Department of Pharmacology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan; Graduate School of Environment and Information Sciences, Yokohama National University, 79-1 Tokiwadai, Hodogaya, Yokohama, Kanagawa 240-8501, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan; Corresponding author
Summary: The consensus for the precise mechanism of action of general anesthetics is through allosteric interactions with GABA receptors in neurons. However, it has been speculated that these anesthetics may also interact with the plasma membrane on some level. Owing to the small size of anesthetics, direct visualization of these interactions is difficult to achieve. We demonstrate the ability to directly visualize a deuterated analog of propofol in living cells using stimulated Raman scattering (SRS) microscopy. Our findings support the theory that propofol is highly concentrated and interacts primarily through non-specific binding to the plasma membrane of neurons. Additionally, we show that SRS microscopy can be used to monitor the dynamics of propofol binding using real-time, live-cell imaging. The strategy used to visualize propofol can be applied to other small molecule drugs that have been previously invisible to traditional imaging techniques