| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
SPOC (spontaneous sarcomeric oscillations) is a characteristic state of the contractile system of striated muscle that exists between the states of relaxation and contraction. We analyzed the SPOC properties in human iPSC-derived cardiomyocytes expressing E101K mutant actin causing hypertrophic cardiomyopathy．Cardiomyocytes expressing E101K mutant showed that the sarcomere length (SL) amplitude decreases by ~37 % compared to cells expressing the wild-type actin. To investigate the molecular mechanism underlying the SL amplitude decrease, E101K mutant actin was expressed by adenovirus vector in the stable C2C12 cell line expressing the adenovirus E1 gene. Actin-activated ATPase measurements using the expressed actins showed that the E101K mutation increased the Kactin for actin 3-fold, whereas the Vmax values were similar. These results suggest that reduction of the actomyosin interaction by E101K actin mutant leads to decreased SL amplitude in the SPOC state.
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