| Project/Area Number |
13557130
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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 | 展開研究 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Niigata University |
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Principal Investigator |
YAMAKURA Tomohiro Niigata University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80272847)
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| Co-Investigator(Kenkyū-buntansha) |
SAKIMURA Kenji Niigata University, Brain Research Institute, Professor, 脳研究科, 教授 (40162325)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Gaseous anesthetics / Glutamate receptor / NMDA receptor / AMPA receptor / Kainate receptor / Acetylcholine receptor / Knock-out mice |
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| Research Abstract |
The effects of gaseous anesthetics on ligand-gated ion channels were investigated. Nitrous oxide (0.58 atmosphere (atm)) and xenon (0.46 atm) exhibited quite similar effects on various receptors. Glycine and GABA_A receptors were potentiated by gaseous anesthetics much less than by isoflurane, while nitrous oxide inhibited GABA_C receptors. Glutamate receptors were inhibited by gaseous anesthetics more markedly than by isoflurane, but less than by ethanol. NMDA receptors were the most sensitive among glutamate receptors, and were inhibited by nitrous oxide by 31%. 5-HT_3 receptors were slightly inhibited by nitrous oxide. The nicotinic acetylcholine (nACh) receptors were inhibited by gaseous and volatile anesthetics, but ethanol potentiated them. The sensitivity was different between α4β2 and α4β2 n ACh receptors ; α4β2 receptors were inhibited by nitrous oxide was non-competitive, and was slightly different depending on membrane potentials for NMDA receptors, but not for nACh receptors. The results of chimeric and point mutant rat nAChRs suggest that a single amino acid residue (β2-V253 or β4-F255) near the middle of the second transmembrane segment determines gaseous anesthetic sensitivity. Mutations of this residue in β subunits and the homologous residue of α4 subunits (α4-V254) showed that this position also determines sensitivities of n AChRs to acetylcholine, isoflurane, pentobarbital, and hexanol. The site-directed mutagenesis of ε2 and ζ1 NMDA receptor subunits showed that the conserved asparagine residue in the second hydrophobic segment M2 of the ζ1 subunit determines gaseous anesthetic sensitivity of NMDA receptors.
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