The elucidation of the mechanism of action of volatile anesthetics based on the relationship between membrane receptor fluidity and signal transduction

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09373
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Kagawa University
• Principal Investigator: Ono Junichiro 香川大学, 医学部, 協力研究員 (90363217)
• Co-Investigator(Kenkyū-buntansha): 樺山 一哉 大阪大学, 大学院理学研究科, 准教授 (00399974) ; 坂内 博子 早稲田大学, 理工学術院, 教授 (40332340) ; 鈴木 辰吾 香川大学, 医学部, 准教授 (50451430)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 揮発性麻酔薬 / 作用機序 / 膜流動性 / シグナル伝達 / ライブセルイメージング

Outline of Final Research Achievements

The mechanisms of action of volatile anesthetics are still unclear. This study aimed to elucidate the mechanism of anesthesia, using the live-cell single-quantum-dot imaging as a feature. An advantage of using quantum-dots is the ability to label receptor proteins in the synaptic cleft. The neuronal cells labeled with quantum-dot were treated with isoflurane, and the dynamics of the receptor on the cell membrane was analyzed. Our results suggest that isoflurane increased the diffusion coefficient of GABAA receptors, and their localization shifted and accumulated within synapses. We also examined the dynamics of AMPA receptors, which play a central role in excitatory synaptic transmission, and found that they showed the similar tendency as GABAA receptors.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

揮発性麻酔薬の作用機序は不明な点が多い。これまでの知見によると、揮発性麻酔薬は生体機能を司るタンパク質に作用することは確実と言える。しかし、揮発性麻酔薬は生体内で同時に複数の系に影響を及ぼす「多部位作用性」という特徴を持つため、作用機序の全貌を掴むことは容易ではない。そこで本課題では、受容体タンパク質への直接作用を解析するというアプローチではなく、生体膜上における受容体の流動性が細胞内へのシグナル伝達に影響を及ぼすという仮説の基に研究を行った。このようなアプローチで麻酔作用機序の解明を進めている研究は他に類を見ない。