| Project/Area Number |
09680759
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MURAKOSHI Takayuki Tokyo Medical and Dental University, Medical School, Associate Professor, 医学部, 助教授 (60190906)
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Tsutomu Tokyo Medical and Dental University, Medical School, Professor, 医学部, 教授 (70183069)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | synaptic transmission / Ca channels / CNS synapses / biogenic amines / transmitter regulation / G-proteins / Caチャネル |
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| Research Abstract |
In order to identify the Ca channel subtype mediating central synaptic transmission and to study the mechanisms of its G-proteins-mediated regulation, whole-cell patch-clamp recordings were performed from pyramidal neurons under observation with Nomarski optics in a slice preparation which was made from the visual cortex of 2- 3-weeks old rats. Glutamatergic excitatory postsynaptic currents (EPSCs) or GABA ergic inhibitory postsynaptic currents (IPSCs) were evoked by stimulation of neighboring pyramidal neurons or interneurons, respectively. EPSC thus evoked was inhibited by omega-conotoxin GVIA, a specific blocker of the N-type Ca channel, in a dose-dependent manner from 30 nM to 1 muM with a maximum reduction of 50%, or by omega-agatoxin IVA, a P/Q-type Ca channel blocker, at 0.3 - 3 muM with a similar maximum recbiction. The amplitude of IPSC was reduced by omega-agatoxin IVA (30 nM - 1 muM) by up to 70 %, whereas the dose-dependent inhibition of the IPSC was not observed by omega-conotoxin GVIA up tol muM The EPSC observed in the same presynaptic and postsynaptic neuronal pair was inhibited by carbachol, noradrenaline and sertonin presynaptically, suggesting that these 3 amine receptors coexist at the presynaptic terminal and that activation of these receptors converge into some step of the regulatory cascade leading to an inhibition of the glutamate release. We then examined aminergic modulation after blocking one of the two Ca channel subtypes by either omega-conotoxin GVLA or omega-agatoxin IVA.The inhibition of the EPSC by each amine was not significantly different between N-type mediated and P/Q-type mediated EPSCs. These findings suggest that there is no preferential linkage between any one of the three aminergic recepotrs and either Ca channel subtype via G-proteins.
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