The physiological role of TASK channel-induced adrenaline secretion

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06865
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Yokohama College of Pharmacy (2020); University of Occupational and Environmental Health, Japan (2018-2019)
• Principal Investigator: Matsuoka Hidetada 横浜薬科大学, 薬学部, 准教授 (90374991)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: TASKチャネル

Outline of Final Research Achievements

I investigated the function and physiological role of TASK1 channels in endocrine cells. Pharmacological and molecular biological analyses showed that TASK1 channels are regulated by the clathrin-dependent endocytosis in NGF- and muscarine-stimulated adrenal medullary and PC12 cells. Furthermore, it showed that muscarine-induced endocytosis of TASK1 channels is regulated through PKC-Pyk2-Src pathway in PC12 cells. Additionally, TASK1 channels were localized at plasma membrane in PC12 cells is due to a lack of p11 protein. On the other hand, the treatment with NGF of PC12 cells was induced the expression of p11 proteins and resulted in a change in membrane localization of TASK1 channels. These results indicate that TASK1 channels were translocated and localized to plasma membrane by dissociating from p11 proteins.

Free Research Field

細胞生理学

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、TASK1チャネルの機能調節機構を明らかにした。ムスカリン受容体によるKチャネルの抑制は、多くのチャネルが、gatingの変化によって制御されていることが知られている。今回申請者は、Kチャネルの1つであるTASK1チャネルの抑制には、gatingの変化だけでなくエンドサイトーシスが関与することを世界で初めて明らかにした。本研究成果は、TASKチャネルファミリーの機能制御機構を明らかにするとともに、未解明の多くのKチャネルの機能制御機構の解明を推進するものと期待され、学術的意義は高い。