| Project/Area Number |
15K19989
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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 |
Orthopaedic surgery
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 活性酸素 / 過酸化水素 / 脊髄損傷 / 二次障害 / パッチクランプ / 脊髄保護療法 / 脊髄保護 / 興奮毒性 / 脊髄前角 / シナプス伝達 / 電位依存性カルシウムチャネル / リアノジン受容体 |
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| Outline of Final Research Achievements |
We investigated how pathological levels of H2O2, an abundant reactive oxygen species, regulate synaptic transmission and neuronal excitability in VH neurons of rats using a whole-cell patch-clamp approach. H2O2 increased the release of glutamate and GABA from presynaptic terminals. The increase in glutamate release involved N-type voltage-gated calcium channels (VGCCs), ryanodine receptors (RyR), and inositol triphosphate receptors (IP3R); the increase in GABA release, which inhibited glutamatergic transmission, involved IP3R. On the other hand, H2O2 decreased neuronal excitability via activation of extrasynaptic GABAA receptors. H2O2 depressed the medium and slow afterhyperpolarisation, suggesting that H2O2 per se has the potential to induce hyperexcitability in VH neurons via a decrease in conductance of small-conductance calcium-activated potassium (SK) channels. Moreover, N-type VGCC inhibitor (ziconotide) attenuated damage induced by spinal cord injury in rat models.
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