1989 Fiscal Year Final Research Report Summary
Patch-clamp studies of glutamate receptor channels in cultured hippocampal neurons.
| Project/Area Number |
60480114
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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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 | 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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| Project Period (FY) |
1985 – 1986
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| Keywords | Glutamate receptor channel / Kainate / Quinolinate / NMDA / Cultured hippocampal neuron / Patch-clamp technique / Single-channel current |
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| Research Abstract |
It is widely accepted that glutamate is the principal neurotransmitter that mediates excitatory synaptic transmission in the mammalian central nervous system. Furthermore, evidence is accumulating that cellular events caused by glutamate play a key role in the induction of plastic changes in the efficacy of the synaptic transmission. Therefore it is important to clarify changes in the membrane properties induced by glutamate and related excitatory amino acids (EAAS) in the central neurons. In this study, we examined the properties of receptor channels activated by EAAs in cultured rat hippocampal neurons. The whole-cell and outside-out configurations of the patch-clamp technique were used to study macroscopic and single-channel currents. The results are summarized as follows:
1. The ions permeant through glutamate receptor channels are Na^+, K^+ and Ca^<2+>.
2. Glutamate activated single channel events of several different levels with single-channel conductances 40-50 pS and < 20 pS. The
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large (40-50 pS) and small (< 20 pS) events were due to the activation of N-methyl-D-aspartate (NMDA) and non-NMDA (quisqualate, or kainate) receptors, respectively.
3. Mg^<21> in the extracellular solution markedly suppressed the opening of NMDA channels in the potential range more negative than -40 mV.
4. The NMDA receptor channel was highly permeable to Ca^<2+>. The value Of P_<ca>/P_<na> was 6.2 according to the constant field equation. The permsability sequence of the NMDA channel among the divalent cations was determined to be Ba^<2+>(1.2) > Ca^<2+>(1.0) > Sr^<2+>(0.8) > Mn^<2+>(O.3)>> Mg^<2+>(<O.02).
5. Quinolinate, an excitotoxic brain metabolite, selectively activated NMDA receptor channels.
6. Kainate receptor channels were classified into two types. The Ca^<2+> permeability of the type 1 receptor was very low. In contrast, the type 2 receptor showed relatively high permeability to Ca^<2+> (P_<ca>/P_<na>=2.3). Study is needed to characterize single-channel properties of the type 2 kainate receptor. Less
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