Functional significance of Ca^<2+>-permeable AMPA-type glutamate receptors in the central nervous system.
| Project/Area Number |
08458265
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
神経・脳内生理学
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| Research Institution | Gunma University |
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Principal Investigator |
OZAWA Seiji Gunma University, School of Medicine, Professor, 医学部, 教授 (40049044)
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| Co-Investigator(Kenkyū-buntansha) |
TSUZUKI Keisuke Gunma University, School of Medicine, Lecturer, 医学部, 講師 (60222139)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | Hippocampal neuron / AMPA receptor / Inward rectification / Ca^<2+> permeability / Type II neuron / Intermediate neuron / Excitatory synaptic transmission / Selective blocker / 競合的逆転写遺伝子増幅法 / 選択的阻害作用 / 合成女郎蜘蛛毒 / 1-ナフチルアセチルスペルミン / 膜電位依存性 |
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| Research Abstract |
AMPA receptors exhibit a marked inward rectification and high Ca^<2+> permeability in a population of cultured rat hippocampal neurons (type II neurons), whereas they exhibit an outwardly rectifying and negligible Ca^<2+> permeability in the majority of neurons (type I neurons). The receptors expressed in type I and type II neurons were designated as type I and type II AMPA receptors, respectively. The purposes of this study were to investigate the distribution of neurons with type II AMPA receptors and to elucidate their functional significances. The results are summarized as follows : 1) A considerable number of type II neurons were found in rat hippocampal slices (14.4% of nonpyramidal neurons). In contrast, the population of type II neurons was quite small in the cerebral cortex (1.8%). In both the hippocampus and the neocortex, however, there were a large number of intermediate neurons that expressed both type I and type II AMPA receptors. 2) Molecular biological studies have indicated that the GluR2 AMPA receptor subunit is not assembled in type II receptors. To analyze molecular basis of the presence of type II and intermediate neurons in the brain, we have established a method for absolute quantification of mRNA of GluR2 subunit at the single cell level. 3) Regarding the functional aspect of type II AMPA receptors, we have shown that they are involved in the fast excitatory neurotransmission in a large number of nonpyramidal neurons in both the hippocampus and the neocortex. 4) To further investigate functional roles of the type II AMPA receptor, pharmacological tools that specifically affect this receptor are needed. We have found that two polyamine derivatives, synthetic joro spider toxin and 1-naphthyl acetyl spermine, selectively suppress type II AMPA receptors with no effect on type I receptors. The dffects of these agents were highly voltage-dependent.
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Report
(3 results)
Research Products
(18 results)
