| Project/Area Number |
04404023
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | KYUSHU UNIVERSITY (1993)
Tohoku University (1992) |
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Principal Investigator |
AKAIKE Norio KYUSHU UNIV., FAC.MED., PROF., 医学部, 教授 (30040182)
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| Co-Investigator(Kenkyū-buntansha) |
HARATA Nobutoshi KYUSHU UNIV., FAC.MED., RES.ASSO., 医学部, 助手
ONO Kyoichi KYUSHU UNIV., FAC.MED., RES.ASSO., 医学部, 助手 (70185635)
MATSUDA Hiroko KYUSHU UNIV., FAC.MED., ASSO.PROF., 医学部, 助教授 (10181736)
鍋倉 淳一 東北大学, 医学部, 助手 (50237583)
河 和善 東北大学, 医学部, 助教授 (70125839)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1992: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Metabotropic glutamate receptors / Nystatin method / Hippocampus / K+ channels / G proteins / Signal transduction / K+チャンネル / 代謝型グルタミン酸受容器 / 興奮性アミノ酸 / 電気生理 / パッチクランプ法 / K^+電流 / 急性単離神経細胞 / 中枢神経 |
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| Research Abstract |
In order to analyze neuronal responses to metabotropic glutamate receptor (mGluR) stimulation, we applied nystatin perforated patch recording to acutely dissociated neurons of immature rats. 1. In CA1 pyramidal neurons, we have found that 1) mGluR activation led to an outward current through opening of Ca2+-dependent K+ channels of intermediate conductance type, 2) the affinity of mGluR for its agonists was 10- to 100-fold higher than that of ionotropic glutamate receptors, 3) the putative mGluR antagonists, AP3 and AP4, did not suppress mGlu responses, 4) mGluR activation is followed by G protein (〕SY.gtoreq.〔) phospholipase C (〕SY.gtoreq.〔) IP3 production (〕SY.gtoreq.〔) Ca2+ release from intracellular stores (〕SY.gtoreq.〔) opening of Ca2+-dependent K+ channels. 2. In CA3 pyramidal neurons, slow inward current was the dominant response, with outward current observed in only 40% of cells. It was clarified that 1) the slow inward current was based on suppression of M current, 2) slow inward currents showed 10-times higher affinity to agonists than outward currents, 3) only the outward currents induced by tACPD (but not by quisqualic acid) were blocked by AP3 and AP4.3. In dentate granule cells, the outward currents had longer duration than those in CA1 and the slow inward current was reversibly suppressed by AP3.4. mGlu response was observed in 80% of the cells from the ventral 1/3 of the CA1 in 1- to 2- week-old rats, but in 40% of the cells from the dorsal 1/3. Frequency of observation was reduced to 40% in the ventral 1/3 and 5% in the dorsal 1/3 when the rats were 3- to 4-week-old.
These results suggest that mGlu responses show regional differences and ontogenetic changes. These diverse actions of mGlu responses are supposed to greatly affect neuronal excitability, an information indispensable for understanding neuronal networks in the CNS.
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