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
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
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 / ハイスループットスクリーニング / イオンチャネル / 活動電位 / 受容体 |
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.
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