| 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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| 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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