| Project/Area Number |
15K15574
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Anesthesiology
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
OKANO Hideyuki 慶應義塾大学, 医学部, 教授 (60160694)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 悪性高熱症 / iPS細胞 / 興奮性神経細胞 / Neurogenin2 / 麻酔薬 / カルシウムイメージング / 骨格筋 / mmRNAトランスフェクション |
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| Outline of Final Research Achievements |
Malignant hyperthermia (MH), is a type of severe reaction that occurs to particular medications used during anesthesia. Symptoms include muscle rigidity, high fever, a fast heart rate, and mixed acidosis. In a large proportion of cases, the propensity for MH is due to a mutation of the type I ryanodine receptor (RYR1), located on the sarcoplasmic reticulum. RYR1 opens in response to increases in intracellular Ca2+ level mediated by L-type calcium channels, thereby resulting in a drastic increase in intracellular calcium levels and muscle contraction. Here, we generated MH iPS cells from blood cells of the patients who have RYR1 gene mutation. MH iPS cells were successfully differentiated into skeletal muscle cells. Several patient cells exhibited muscle rigidity-like alteration and high concentration of lactate in the culture supernatant. Also accumulated RYR1 puncta were detected in the patient muscle cells. These findings can propose a new cellular model of MH.
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