Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Outline of Final Research Achievements |
In this project, we aimed to understand the mutant RyR2-related arrhythmogenic mechanism and to establish a screening procedure for RyR2 inhibitors as anti-arrhythmic drugs. First, functional evaluation of RyR2 mutations were carried out using HEK cell expression system and a cardiomyocyte cell line. We found gain-of-function type and loss-of-function type of arrhythmogenic mutations. In the former, our functional analysis has proved to be very useful for predicting the severity of diseases caused by the mutations. Next, we developed a screening system for specific RyR2 inhibitors utilizing the ER Ca2+ monitoring, which was found to be an accurate indicator of RyR2 activity.
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