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Functional analysis of KCC2 in the animal model showing resistance to sedative drug

Research Project

Project/Area Number 16K10945
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionYokohama City University

Principal Investigator

Andoh Tomio  横浜市立大学, 医学研究科, 客員教授 (00193110)

Co-Investigator(Kenkyū-buntansha) 宮崎 智之  横浜市立大学, 医学部, 准教授 (30580724)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsKCC2 / CLP290 / ミダゾラム / 麻酔薬 / 鎮静 / 幼弱動物 / 学習
Outline of Final Research Achievements

By administering CLP290, intracellular chloride ion is pumped out of the cell and the extracellular chloride ion concentration becomes relatively high. In the present study, it was found that CLP290 increases phosphorylation of KCC2, which regulates intracellular chloride ion concentration. When a GABA receptor agonist is administered in this state, chloride ions are introduced into the cells from outside the cell, which has a high concentration, following activation of the GABA receptor, and nerve cell activation is suppressed. In this study, this phenomenon was clarified by immunohistological examination using pCREB. It was revealed that these cell biological changes cause sedation at the individual level. In this study, we investigated this phenomenon using the direct reflection.

Academic Significance and Societal Importance of the Research Achievements

カリウム-塩素イオン共輸送担体を介したchloride homeostasisが幼若動物の鎮静に与える役割を明らかにし、さらにはそのメカニズムに着目した鎮静耐性改善薬としての臨床応用可能性を探るものである。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (1 results)

All 2016

All Presentation (1 results)

  • [Presentation] 新生児動物の鎮静におけるKCC2の機能解析2016

    • Author(s)
      池田舞子, 宮崎智之, 米崎久美子, 小山行秀, 安藤富男, 後藤隆久
    • Organizer
      第63回日本麻酔科学会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-12-27  

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