Lipid raft-based mechanism of the local anesthetic action

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06590
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: Kyushu University
• Principal Investigator: Kinoshita Masanao 九州大学, 理学研究院, 助教 (40529517)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脂質ラフト / 局所麻酔薬 / 蛍光脂質プローブ / 蛍光分光測定 / 細胞膜

Outline of Final Research Achievements

Lipid rafts are ordered membrane domains, which work as a platform for signal transduction. Recently, our group disclosed that local anesthetics suppress the formation of the raft-like ordered domains using model membranes.
However, it is unknown whether similar results are obtained in the real cell membranes. In this study, we examined influence of local anesthetics on the lipid rafts formed in neuroblastoma cell (Neuro 2A). Firstly, lipid rafts and fluid membrane matrix were separately labeled by fluorescent lipid probes, which form a favorable Forster resonance energy transfer (FRET) pair. Interestingly, exogenous addition of local anesthetics led to increase in the FRET, indicating the enhanced miscibility of the raft and fluid matrix. Moreover, local anesthetics reversibly enhanced diffusion coefficient of lipid rafts. Since diffusion coefficients corelated inversely with the domain size, this result indicated that local anesthetics suppress the formation of lipid rafts.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

これまで局所麻酔薬の作用機序はイオンチャネルとの直接的な相互作用に帰着されてきた。一方、本研究では局所麻酔薬が脂質ラフトに作用することでチャネルを不活性化させるという、ラフト標的仮説を支持する結果を得た。ここで得られた知見は、より効率的な局所麻酔薬の創薬に向けた、新たな指針を提示する。