Developement of a novel screening system for drugs acting on ion channels based on measurement of cell death

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670039
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: Imaizumi Yuji 名古屋市立大学, 薬学研究科(研究院), 教授 (60117794)
• Co-Investigator(Kenkyū-buntansha): YAMAMURA Hisao 名古屋市立大学, 大学院薬学研究科, 准教授 (80398362) ; SUZUKI Yoshiaki 名古屋市立大学, 大学院薬学研究科, 助教 (80707555)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 薬理学 / 薬学 / 創薬 / スクリーニング / 電位依存性Na+チャネル / 内向き整流性K+チャネル / 細胞死 / パッチクランプ法

Outline of Final Research Achievements

In the present study, we developed a novel screening system for drugs acting on ion channels. The achievements of results in this study are as follows;
(1) We established a recombinant cell line co-expressing mutant Nav1.5 and　Kir2.1 (IFM/Q3+Kir). Electrical stimulation (ES) of the cell line induced prolonged action potentials and subsequent cell death. Furthermore "third" ion channel (Kv,K2P or α7-nicotinic receptor) that are candidates for therapeutic targets was expressed in IFM/Q3+Kir. In these cells, drugs that modulate the third ion channel activity can change the mortality of the cells after ES. MTT assay using already-known drugs acting on the "third" ion channels demonstrated that dose-response curves obtained from our new system are as accurate as those obtained from patch-clamp recordings.
(2) We developed a new device that enables us to stimulate the recombinant cell lines　cultured on 96 well plates with ES. Thus, our new system is available for high throughput screening.

Free Research Field

薬理学