Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Outline of Final Research Achievements |
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal arrhythmia mainly caused by single point mutations in cardiac ryanodine receptor (RyR2). These mutations are distributed in three hot spots (N-terminal, central and C-terminal) of RyR2. Diastolic calcium (Ca) leak via RyR2 can cause ventricular arrhythmia such as CPVT. We have already showed that reduced calmodulin (CaM)-RyR2 affinity destabilizes RyR2 channel, and causes Ca leak in a central RyR2-CPVT Knock-in (KI) mouse (R2474S/+). To further understand the pathophysiology of RyR2 mutation on CaM-RyR2 affinity in N-terminal RyR2-CPVT KI mouse (R176Q/+) and C-terminal RyR2-CPVT KI mouse (R4496C/+), Our results suggest that reduced CaM-RyR2 affinity causes Ca leak in N-terminal RyR2-CPVT mutation, but C-terminal RyR2-CPVT mutation causes Ca leak independent of CaM-RyR2 affinity.
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