| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Mitsugumin 23 (MG23) is a 23 kDa transmembrane protein localized to the sarcoplasmic reticulum (SR) and nuclear membranes in a variety of cells. After reconstitution into phospholipid bilayers, MG23 behaved as a voltage-dependent cation channel, permeable to both K+ and Ca2+. Under voltage-clamp conditions, Zn2+ (>2 nM) caused dysregulated RyR2 openings and also revealed that RyR2 are not the only SR Ca2+-permeable channels regulated by Zn2+. Elevating the cytosolic Zn2+ concentration to 1 nM increased the activity of the MG23. The current amplitude of the MG23 full-open state was consistent with that previously reported for RyR2 sub-conductance gating, suggesting that in heart failure in which Zn2+ levels are elevated, RyR2 do not gate in a sub-conductance state, but rather MG23-gating becomes more apparent. These data suggest that dysregulated Zn2+ homeostasis alters the function of both RyR2 and MG23 and that both ion channels play a key role in diastolic SR Zn2+ leakage.
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