Abnormal GABA neurotransmission in a Kcnq2 model of early onset epilepsy
| Project/Area Number |
26870781
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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 |
Pediatrics
Embryonic/Neonatal medicine
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| Research Institution | University of Miyazaki (2016-2017)
Fukuoka University (2014-2015) |
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Principal Investigator |
Uchida Taku 宮崎大学, 医学部, 助教 (60464137)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 小児てんかん / 電位依存性カリウムイオンチャネル / KCNQ2 / GABA作動性神経細胞 / ノックインマウス / 電気生理 / パッチクランプ / 新生児てんかん / 発達小児科学 / 電気生理学 / GABA作動性神経細 / 新生児医学 / ＫＣＮＱ２ / てんかん |
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| Outline of Final Research Achievements |
Mutations of the KCNQ2 gene, which encodes the Kv7.2 subunit of voltage-gated M-type potassium channels (M-channels), have been associated with epilepsy in the neonatal period. Neonatal brain is unique in that the neurotransmitter GABA triggers excitatory action.To examine whether KCNQ2-related neuronal hyperexcitability involves neonatally excitatory GABA, we examined one-week-old knock-in mice expressing the Kv7.2 variant p.Tyr284Cys (Y284C). Brain slice electrophysiology revealed elevated CA1 hippocampal GABAergic interneuron activity with respect to presynaptic firing and postsynaptic current frequency. Blockade with the GABAA receptor antagonist bicuculline decreased ictal bursting in divalent ion-challenged brain slices, which is consistent with GABA mediating an excitatory function that contributes to the hyperexcitability observed in mutant animals. We conclude that excitatory GABA contributes to the phenotype in these animals.
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Report
(5 results)
Research Products
(13 results)
