Elucidation of the mechanism of action of volatile anesthetics by visualization of membrane microdomains and receptors

• Project/Area Number: 15K10514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• 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, 理学研究科, 准教授 (00399974)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Shingo 香川大学, 医学部, 准教授 (50451430)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 揮発性麻酔薬 / 作用機序 / ライブセルイメージング / FRAP解析 / マイクロドメイン / 膜流動性 / シグナル伝達 / 麻酔科学 / 麻酔メカニズム / FRAP / TIRF / マイクロ流体デバイス / 麻酔学

Outline of Final Research Achievements

We studied the mechanism of action of volatile anesthetics using live cell imaging. Especially, fluorescence recovery after photobleaching (FRAP) enables characterization of quantitative dynamic properties in living cells. We visualized membrane microdomains and receptors using HaloTag fusion proteins for the FRAP analysis. The fluidity of HaloTag fused transferrin receptors, a marker of the non-microdomain fraction, was augmented by isoflurane exposure. Whereas, no significant difference was detected in the HaloTag fused GPI anchor proteins. Since lateral diffusion of transmembrane proteins such as transferrin receptors influences signal transduction, it is considered that enhanced lateral diffusion by volatile anesthetics may contribute to the mechanism of action.

Research Products

• [Journal Article] Effect of the volatile anesthetic agent isoflurane on lateral diffusion of cell membrane proteins (2018)
  • Author(s): Junichiro Ono, Satoko Fushimi, Shingo Suzuki, Kiyoshi Ameno, Hiroshi Kinoshita, Gotaro Shirakami, Kazuya Kabayama
  • Journal Title: FEBS Open Bio Volume: - Issue: 7 Pages: 1127-1134
  • DOI: 10.1002/2211-5463.12443
  • Peer Reviewed / Open Access
• [Presentation] イソフルランは生細胞のインスリン受容体の流動性に可逆的変化を与える (2017)
  • Author(s): 小野純一郎，佐野 愛，白神 豪太郎，新井 健太，木村 啓志，樺山 一哉
  • Organizer: 日本麻酔科学会第64回学術集会
• [Presentation] イソフルランが生細胞の脂質ラフトの動態に与える影響 (2015)
  • Author(s): 小野純一郎、白神豪太郎
  • Organizer: 日本麻酔科学会第62回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-05-28