• Title/Summary/Keyword: AMPA

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Effect of Antioxidant and Ampa/kainate Receptor Antagonist on Cerebral Neurons Damaged by Ischemia (허혈이 유도된 대뇌신경세포에 대한 항산화제 및 Ampa/kainate 수용체 길항제의 영향)

  • Oh, Yeon-Kyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.4
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    • pp.1022-1026
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    • 2005
  • To clarify the toxic effect on cultured neonatal mouse cerebral neurons damaged by ischemia, we examined the cytotoxicity induced by ischemia and the protective effect of antioxidant and AMPA/kainate receptor antagonist against ischemia-induced cytotoxicity on cultured cerebral neurons. For this study, mice were administrated with 20ug/kg cyclothiazide or 50U/kg vitamin E via intraperitoneal injection for 2 hours before ischemic induction. After cell culture for 7 days, cell viability, amount of neurofilament and protein kinase C activity were examined. Ischemia decreased significantly cell viability, amount of neurofilament and the increase of protein kinase C activity in these cultures. In the protective effect, vitamin I showed remarkably the increase of cell viability and amount of neurofilament, and the decrease of protein kinase C activity but, cyclothiazide did not showed any protective effect on ischemia-induced cytotoxicity. From these results, it is suggested that vitamin I is effective in blocking the neurotoxicity induced by ischemia, but cyclothiazide as a AMPA/kainate receptor antagonist is not.

Immunohistochemical detection of GluA1 subunit of AMPA receptor in the rat nucleus accumbens following cocaine exposure

  • Cai, Wen Ting;Han, Joonyeup;Kim, Wha Young;Kim, Jeong-Hoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.1
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    • pp.79-85
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    • 2021
  • α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are differentially regulated in the nucleus accumbens (NAcc) of the brain after cocaine exposure. However, these results are supported only by biochemical and electrophysiological methods, but have not been validated with immunohistochemistry. To overcome the restriction of antigen loss on the postsynaptic target molecules that occurs during perfusion-fixation, we adopted an immersion-fixation method that enabled us to immunohistochemically quantify the expression levels of the AMPA receptor GluA1 subunit in the NAcc. Interestingly, compared to saline exposure, cocaine significantly increased the immunofluorescence intensity of GluA1 in two sub-regions, the core and the shell, of the NAcc on withdrawal day 21 following cocaine exposure, which led to locomotor sensitization. Increases in GluA1 intensity were observed in both the extra-post synaptic density (PSD) and PSD areas in the two sub-regions of the NAcc. These results clearly indicate that AMPA receptor plasticity, as exemplified by GluA1, in the NAcc can be visually detected by immunohistochemistry and confocal imaging. These results expand our understanding of the molecular changes occurring in neuronal synapses by adding a new form of analysis to conventional biochemical and electrophysiological methods.

Increases in Effective Cleft Glutamate Concentration During Expression of LTP

  • Jung, Su-Hyun;Choi, Suk-Woo
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.2
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    • pp.113-119
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    • 2002
  • Long-term potentiation (LTP) at hippocampal CA3-CA1 synapses is often associated with increases in quantal size, traditionally attributed to enhanced availability or efficacy of postsynaptic glutamate receptors. However, augmented quantal size might also reflect increases in neurotransmitter concentration within the synaptic cleft since AMPA-type glutamate receptors are not generally saturated during basal transmission. Here we report evidence that peak cleft glutamate concentration $([glu]_{cleft})$ increases during LTP, as indicated by a lessening of the blocking effects of rapidly unbinding antagonists of AMPA. The efficacy of slowly equilibrating antagonists remained unchanged. The elevated $[glu]_{cleft}$ helps support the increased quantal amplitude of AMPA-type EPSCs (excitatory postsynaptic currents) during LTP.

NMDA-type Glutamatergic Modulation in Dopaminergic Activation Measured by Apomorphine-Induced Cage Climbing Behaviors

  • Jang, Choon-Gon;Lee, Seok-Yong
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.613-617
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    • 2001
  • The present study examined the hypothesis that NMDA, AMPA/Kainate, and metabotropic (mGlu) glutamate receptors contribute to a behavioral stimulation induced by activation of dopamine receptors by comparing responses in apomorphine-induced cage climbing behaviors in mice. MK-801, CNQX, and MCPG were served as the NMDA receptor, AMPA/Kainate receptor, and mGlu receptor antagonist, respectively, to elucidate the glutamatergic modulation in apomorphine-induced eopaminergic activation in mice. Drugs were administered intracerebroventricularly (i.c.v.) into the mouse brain 15 min before the apomorphine treatment (2 mg/kg, s.c.). 1.c.v. injection of MK-801 inhibited the apomorphine-induced cage climbing behavior dose-dependently. However, treatments with CNQX and MCPG did not any significant change in apomorphine-induced cage climbing behavior in mice. These results suggest that stimulation of NMDA type of glutamate receptors could contribute to the dopaminergic sti mutation, but not AMPA/Kainate and mGlu type glutamate receptors.

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Glutamate Receptor-interacting Protein 1 Protein Binds to the Armadillo Family Protein p0071/plakophilin-4 in Brain (Glutamate receptor-interacting protein 1 단백질과 armadillo family 단백질 p0071/plakophilin-4와의 결합)

  • Moon, Il-Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1055-1061
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    • 2009
  • ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are widespread throughout the central nervous system and appear to serve as synaptic receptors for fast excitatory synaptic transmission mediated by glutamate. Their modulation is believed to affect learning and memory. To identify the interaction proteins for the AMPA receptor subunit glutamate receptor-interacting protein 1 (GRIPl), GRIP1 interactions with armadillo family protein p0071/plakophilin-4 were investigated. GRIP1 protein bound to the tail region of p0071/plakophilin-4 but not to other armadillo family protein members in a yeast two-hybrid assay. The "S-X-V" motif at the carboxyl (C)-terminal end of p0071/plakophilin-4 is essential for interaction with GRIP1. p0071/plakophilin-4 interacted with the Postsynaptic density-95/Discs large/Zona occludens-1 (PDZ) domains of GRIPI in the yeast two-hybrid assay, as is indicated also by Glutathione S-transferase (GST) pull-down, and co-immunoprecipitated with GRIP1 antibody in brain fraction. The findings of this study provide evidence that p0071/plakophilin-4 is an interactor of GRIP1.

Distribution of Glutamate Receptors in the Retina of the Greater Horseshoe Bat (Rhinolophus ferrumequinum) (한국관박쥐 망막에서 글루타메이트 수용체의 분포 양상)

  • Kwon, Oh-Ju;Jeon, Chang-Jin
    • Journal of Korean Ophthalmic Optics Society
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    • v.19 no.3
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    • pp.413-418
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    • 2014
  • Purpose: The objective of this study was analyzing the distribution of the excitatory neurotransmitter glutamate receptor to investigate the function in the retina of the greater horseshoe bat. Methods: After retinal tissues of adult greater horseshoe bat were cut into $40{\mu}m$ vertical sections, standard immuno-cytochemical techniques was applied for analysis. Immunofluorescence images were obtained using the Bio-Rad MRC 1024 laser scanning confocal microscope. Results: AMPA (GluR1-4), Kainate (GluR5-7, KA1-2) and NMDA (1, 2A, 2B) mainly distributed in the inner plexiform layer and outer plexiform layer. KA1 receptors have existed not only plexiform layer but also ganglion cell layer. Conclusions: The greater horseshoe bat has same neuron and neurotransmitter to mammalian retina. These findings suggest that bat has a functional retina for visual analysis.

A Possible Role of Kainate Receptors in C2C12 Skeletal Myogenic Cells

  • Park, Jae-Yong;Han, Jae-Hee;Hong, Seong-Geun
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.6
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    • pp.375-379
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    • 2003
  • $Ca^{2+}$ influx appears to be important for triggering myoblast fusion. It remains, however, unclear how $Ca^{2+}$ influx rises prior to myoblast fusion. Recently, several studies suggested that NMDA receptors may be involved in $Ca^{2+}$ mobilization of muscle, and that $Ca^{2+}$ influx is mediated by NMDA receptors in C2C12 myoblasts. Here, we report that other types of ionotropic glutamate receptors, non-NMDA receptors (AMPA and KA receptors), are also involved in $Ca^{2+}$ influx in myoblasts. To explore which subtypes of non-NMDA receptors are expressed in C2C12 myogenic cells, RT-PCR was performed, and the results revealed that KA receptor subunits were expressed in both myoblasts and myotubes. However, AMPA receptor was not detected in myoblasts but expressed in myotubes. Using a $Ca^{2+}$ imaging system, $Ca^{2+}$ influx mediated by these receptors was directly measured in a single myoblast cell. Intracellular $Ca^{2+}$ level was increased by KA, but not by AMPA. These results were consistent with RT-PCR data. In addition, KA-induced intracellular $Ca^{2+}$ increase was completely suppressed by treatment of nifedifine, a L-type $Ca^{2+}$ channel blocker. Furthermore, KA stimulated myoblast fusion in a dose-dependent manner. CNQX inhibited not only KA-induced myoblast fusion but also spontaneous myoblast fusion. Therefore, these results suggest that KA receptors are involved in intracellular $Ca^{2+}$ increase in myoblasts and then may play an important role in myoblast fusion.

Responsiveness of Dendrites to the Glutamate Applied Focally with Pressure Ejector and Iontophoresis into Hippocampal Slices

  • Kim, Jin-Hyuk;Shin, Hong-Kee;Chang, Hyun-Ju;Kim, Hye-Young
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.6
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    • pp.457-466
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    • 2001
  • Glutamate is the most common excitatory amino acid in the brain. Responsiveness of dendrites to the glutamate greatly varies depending on the application sites. Especially, a point of the maximal response to the glutamate of the dendrite is called as 'hot spot'. In our experiment, the responsiveness of the hot spot to the glutamate was investigated in the CA1 pyramidal neuron of the rat hippocampal slice. CNQX, the antagonist of AMPA receptor, blocked 95% of membrane current to the glutamate focal application $(I_{gl}).$ Train ejection of glutamate on one point of the dendrite increased or decreased the amplitude of $I_{gl}$ with the pattern of train, and the changes were maintained at least for 30 min. In some cases, glutamate train ejection also induced calcium dependent action potentials. To evoke long-term change of synaptic plasticity, we adopted ${\theta}-burst$ in the glutamate train ejection. The ${\theta}-burst$ decreased the amplitude of glutamate response by 60%. However, after ${\theta}-burst$ glutamate train ejection, the calcium dependent action potential appeared. These results indicated that the focal application of glutamate on the neuronal dendrite induced response similar to the synaptic transmission and the trains of glutamate ejection modulated the change of AMPA receptor.

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Distribution of AMPA Glutamate Receptor GluR1 Subunit-immunoreactive Neurons and their Co-Localization with Calcium-binding Proteins and GABA in the Mouse Visual Cortex

  • Kim, Tae-Jin;Ye, Eun-Ah;Jeon, Chang-Jin
    • Molecules and Cells
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    • v.21 no.1
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    • pp.34-41
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    • 2006
  • The neuronal localization of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor (GluR) subunits is vital as they play key roles in the regulation of calcium permeability. We have examined the distribution of the calcium permeable AMPA glutamate receptor subunit GluR1 in the mouse visual cortex immunocytochemically. We compared this distribution to that of the calcium-binding proteins calbindin D28K, calretinin, and parvalbumin, and of GABA. The highest density of GluR1-immunoreactive (IR) neurons was found in layers II/III. Enucleation appeared to have no effect on the distribution of GluR1-IR neurons. The labeled neurons varied in morphology; the majority were round or oval and no pyramidal cells were labeled by the antibody. Two-color immunofluorescence revealed that 26.27%, 10.65%, and 40.31% of the GluR1-IR cells also contained, respectively, calbindin D28K, calretinin, and parvalbumin. 20.74% of the GluR1-IR neurons also expressed GABA. These results indicate that many neurons that express calcium-permeable GluR1 also express calcium binding proteins. They also demonstrate that one fifth of the GluR1-IR neurons in the mouse visual cortex are GABAergic interneurons.

Development of Metal Composite Powder Non-corrosive Flux for Low Temperature Forming of the Aluminum Brazing Filler Material (비부식성 플럭스를 이용한 알루미늄 브레이징용 필러 소재의 저온 성형용 금속 복합 분말 개발)

  • Kim, Dae-Young;Jang, Ha-Neul;Yoon, Dae-Ho;Shin, Yun-Ho;Kim, Seong-Ho;Choi, Hyun-Joo
    • Journal of Powder Materials
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    • v.26 no.1
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    • pp.16-21
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    • 2019
  • In aluminum brazing processes, corrosive flux, which is used in preventing oxidation, is currently raising environmental concerns because it generates many pollutants such as dioxin. The brazing process involving non-corrosive flux is known to encounter difficulties because the melting temperature of the flux is similar to that of the base material. In this study, a new brazing filler material is developed based on aluminum and non-corrosive flux composite powder. To minimize the interference of consolidation aluminum alloy powder by the flux, the flux is intentionally embedded in the aluminum alloy powder using a mechanical milling process. This study demonstrates that the morphology of the composite powder can be varied according to the mixing process, and this significantly affects the relative density and mechanical properties of the final filler samples.