The development of a diagnostic method for detecting heart defects based on spontaneous sarcomeric oscillations (SPOC) profiles from human iPS cell-derived cardiomyocytes

2014 Fiscal Year Final Research Report

• Project/Area Number: 24650213
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology and muscle physiology
• Research Institution: Waseda University
• Principal Investigator: OHKI TAKASHI 早稲田大学, 理工学術院, 講師 (80443480)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 心筋 / 筋収縮 / SPOC / アデノウイルス / 拡大型心筋症

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.

Free Research Field

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