| Project/Area Number |
17K16128
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Yokohama City University |
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Principal Investigator |
Kunii Misako 横浜市立大学, 附属病院, 助教 (80725200)
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| Research Collaborator |
Tanaka Fumiaki
Matsumoto Naomichi
Doi Hiroshi
Hashiguchi Syunta
Ohba Chihiro
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | CACNA1G / VGCC / てんかん / 発達障害 / チャネル病 / パッチクランプ / T-type VGCC / CaV3.1 / patch-clamp / パッチクランプ法 / 電位依存性カルシウムチャネル / 遺伝性脊髄小脳変性症 |
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| Outline of Final Research Achievements |
We find three patients with neurodevelopmental disorders harboring de novo CACNA1G mutations.Two of three mutations were reported as childhood-onset cerebellar atrophy (Chemin et al., 2018). To investigate the effect of CaV3.1 mutations on channel function, the WT and each mutant CaV3.1 channel were expressed in HEK-293T cells, and the T-type Ca2+ current was studied with the standard whole-cell patch-clamp technique.I-V curve, activation and steady-state inactivation curves, and tau kinetics were changed in these known mutations.These results were almost the same as previous report. Further, we assessed the electrical resonance of WT and mutant CaV3.1 channels.Now we are preparing for the publishing our report describing clinical phenotypes of the patients with these mutations and findings on channel function obtained by whole-cell voltage-clamp analysis.
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| Academic Significance and Societal Importance of the Research Achievements |
3種類の変異のうち昨年報告された2種類は白人における症例であり，アジア人での報告はまだない．また，同一変異ではあるが臨床所見も一部既報告とは異なる部分がある．CACNA1G変異による疾患の臨床症状の多様さを示しており，さらに未報告の変異1例も含んでおり報告の意義がある．さらに，既報告で行われている一般的な電気生理学的解析のみではなく，共振という電気生理学的現象に着目し，実験を追加した．共振はこれまで各種細胞の特性を明らかにするため着目されてきたが，疾患原因となる変異をもつチャネルでの検討はほとんどなされていない．今後のチャネル病の解明にも有用な手法であり，有用な報告である．
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