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

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10945
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Yokohama 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
• Keywords: KCC2 / CLP290 / ミダゾラム

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.

Free Research Field

麻酔科学

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。