| Project/Area Number |
09044260
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
General physiology
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| Research Institution | University of Tokyo |
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Principal Investigator |
TAKAHASHI Tomoyuki University of Tokyo Graduate School of Medicine Professor, 大学院・医学系研究科, 教授 (40092415)
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| Co-Investigator(Kenkyū-buntansha) |
CUTTLE M.f. University of Leicester Faculty of Medicine Research Associate, 医学部, 助手
FORSYTHE I.D University of Leicester Faculty of Medicne Associate Professor, 医学部, 助教授
TSUJIMOTO Tetsuhiro University of Tokyo Graduate School of Medicine Research Associaite, 大学院・医学系研究科, 助手 (40212055)
ONODERA Kayoko University of Tokyo Graduate School of Medicine Lecturer, 大学院・医学系研究科, 講師 (00053091)
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| Project Period (FY) |
1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1997: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | synaptic transmission / synaptic plasticity / transmitter / calcium channel / Gprotein / slice / patch-clamp / receptor |
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| Research Abstract |
We made direct recordings from a giant presynaptic terminal called as the calyx of Held and a postsynaptic target cell in the medial nucleus of the trapezoid body (MNTB) in rat brain stem slice. The metabotropic glutamate receptor (mGluR) agonist L-AP4 reversibly suppressed EPSCs recorded from the MNTB neurons. Similarly the GABA_B receptor agonist baclofen suppressed EPSCs. Both agonists were found to suppress Ca current recorded from the preterminal, whereas had no effect on the presynaptic voltage-dependent potassium current. The reduction of EPSCs by L-AP4 or baclofen could be fully explained by the reduction of presynaptic Ca. We conclude that mGluR or GABA_B receptor agonists suppress presynaptic Ca channel thereby reducing transmitter release.
This presynaptic ca channel was pharmacologically identified as P-type. The presynaptic P-type Ca channel showed a marked inactivation when it was evoked by a brief depolarizing pulse at high frequency or when a depolarization was prolonged. This inactivation was dependent upon external Ca concentration and was largest when Ca current was largest. The inactivation was not much attenuated by intracellular loading of BAPTA or replacement of charge carrier Ca by Sr or Ba, but was abolished when external divalent cations were entirely replaced by Na. Thus, the inactivation mechanism is divalent cation current dependent, suggesting that the locus of block is close to or inside the Ca channel pore. When EPSCs were evoked by presynaptic Ca current (IpCa) induced by a brief depolarizing pulse, tetanic stimulation produced a profound synaptic depression followed by a gradual recovery. During the recovery, IpCa also recovered from inactivation and the recovery of EPSCs was fully explicable quantitatively by the recovery of IpCa. We conclude that presynaptic Ca current inactivation contributes to post-tetanic synaptic depression.
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