• 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.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.1-7
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• 1999

Background: To study the role of spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in pain behaviors caused by mild burn, we examined the effect of intrathecal administered ACEA 2085, which has been recently characterized as a high potency competitive AMPA receptor antagonist, on the thermal hyperalgesia state induced by mild burn. Methods: A thermal injury was induced by applying the left hind paw to a thermal surface ($52.5^{\circ}C$) for 45 sec. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus. Thirty min after thermal injury, the paw withdrawal latency (PWL) in injured paw of all groups fell from 10~12 sec to 5~7 sec. At that time, ACEA 2085 (0.01~0.1 mcg) and 6-cyano-7-nitroquinoxalinedione (CNQX, 1~30 mcg) were injected through intrathecal heters in rats with mild burn injury on the right hindpaw. And then, PWL were measured in the both hindpaw every 30 minutes for about three hours. Results: The intrathecal injection of ACEA 2085 produced a dose dependent reversal of the hyperalgesia in the right hindpaw and more potent than CNQX, but had no effect upon the response latency of the normal left hind paw even at the largest doses. All effects were observed at doses that had no significant effect upon motor function. Conclusions: Intrathecal ACEA 2085, highly selective AMPA receptor antagonist produce a dose- dependent reversal of the thermal hyperalgesia evoked mild burn injury. These results suggested that spinal AMPA receptor play an important role in the hyperalgesia induced by mild burn injury.

• 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.

• 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.

• Journal of Life Science
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• v.25 no.10
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• pp.1103-1109
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• 2015

Cholinergic innervation of the hippocampus is known to be correlated with learning and memory. The cholinergic agonist carbachol (CCh) modulate synaptic plasticity and produced long-term synaptic depression (LTD) in the hippocampus. However, the exact mechanisms by which the cholinergic system modifies synaptic functions in the hippocampus have yet to be determined. This study introduces an acetylcholine receptor-mediated LTD that requires internalization of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors on the postsynaptic surface and their intracellular mechanism in the hippocampus. In the present study, we showed that the application of the cholinergic agonist CCh reduced the surface expression of GluA2 on synapses and that this reduction was prevented by the M1 muscarinic acetylcholine receptor antagonist pirenzepine in primary hippocampal neurons. The interaction between GluA2 and the glutamate receptor-interacting protein 1 (GRIP1) was disrupted in a hippocampal slice from a rat upon CCh simulation. Under the same conditions, the binding of GluA2 to adaptin-α, a protein involved in clathrin-mediated endocytosis, was enhanced. The current data suggest that the activation of LTD, mediated by the acetylcholine receptor, requires the internalization of the GluA2 subunits of AMPA receptors and that this may be controlled by the disruption of GRIP1 in the PDZ ligand domain of GluA2. Therefore, we can hypothesize that one mechanism underlying the LTD mediated by the M1 mAChR is the internalization of the GluA2 AMPAR subunits from the plasma membrane in the hippocampal cholinergic system.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.996-1001
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• 2003

It is well known that oxidative stress of reactive oxygen species(ROS) may be a causative factor in the pathogenesis of bone disorder. The purpose of this study was to evaluate the cytotoxicity of oxidative stress. Cell viability by MTS assay or INT assay, activity of glutathione peroxidase(GPx), lipid peroxidation(LPO) activity and cell viablity. And also protctive effect of glutamate receptors against ROS-induced osteotoxicity was examined by protein synthesis, alkaline phosphatase (ALP) activity and lactate dehydrogenase (LDH) activity in cultured rat osteoblasts and osteoclasts. XO/HX decreased cell viability and GPx activity, protein synthesis and ALP activity, but increased LPO activity and LDH activity. In the protective effect, N-methyl-D-aspartate (NMDA) receptor antagonists or AMPA/kainate receptor antagonists such as D-2-amino-5-phosphonovaleric acid (APV), 7-chlorokynurenic acid (CKA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX), NMDA receptor antagonists but AMPA/kainate receptor antagonists showed protective effect on xanthine oxidase (XO) and hypoxanthine (HX) in these cultures by the increse of protein synthesis, ALP activity.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.53-57
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• 2003

The glutamate receptors (GluRs) are key receptors for modulatory synaptic events in the central nervous system. It has been reported that glutamate increases the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) and induces cytotoxicity. In the present study, we investigated whether the glutamate-induced $[Ca^{2+}]_i$ increase was associated with the activation of ionotropic (iGluR) and metabotropic GluRs (mGluR) in substantia gelatinosa neurons, using spinal cord slice of juvenile rats (10${\sim}21 day). $[Ca^{2+}]_i$ was measured using conventional imaging techniques, which was combined with whole-cell patch clamp recording by incorporating fura-2 in the patch pipette. At physiological concentration of extracellular $Ca^{2+}$, the inward current and $[Ca^{2+}]_i$ increase were induced by membrane depolarization and application of glutamate. Dose-response relationship with glutamate was observed in both $Ca^{2+}$ signal and inward current. The glutamate-induced $[Ca^{2+}]_i$ increase at holding potential of -70 mV was blocked by CNQX, an AMPA receptor blocker, but not by AP-5, a NMDA receptor blocker. The glutamate-induced $[Ca^{2+}]_i$ increase in $Ca^{2+}$ free condition was not affected by iGluR blockers. A selective mGluR (group I) agonist, RS-3,5-dihydroxyphenylglycine (DHPG), induced $[Ca^{2+}]_i$ increase at holding potential of -70 mV in SG neurons. These findings suggest that the glutamate-induced $[Ca^{2+}]_i$ increase is associated with AMPA-sensitive iGluR and group I mGluR in SG neurons of rats.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.425-432
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• 2016

In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current ($I_{NMDA}$) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic $I_{NMDA}$ in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate INMDA facilitates the ${\alpha}$-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In $low-Mg^{2+}$ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in $I_{holding}$ ($I_{GLU}$) at a holding potential ($V_{holding}$) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive $I_{GLU}$ was observed even in normal aCSF at $V_{holding}$ of -40 mV or -20 mV. $I_{GLU}$ was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in $I_{holding}$ ($I_{AMPA}$) in SON MNCs. Pretreatment with AP5 attenuated $I_{AMPA}$ amplitudes to ~60% of the control levels in $low-Mg^{2+}$ aCSF, but not in normal aCSF at $V_{holding}$ of -70 mV. $I_{AMPA}$ attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced $I_{AMPA}$ attenuation in SON MNCs. Finally, chronic dehydration did not affect $I_{AMPA}$ attenuation by AP5 in the neurons. These results suggest that tonic $I_{NMDA}$, mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.

• Proceedings of the Botanical Society of Korea Conference
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• 2001.04a
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• pp.11-11
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• 2001

• Journal of Life Science
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• v.15 no.3 s.70
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• pp.505-512
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• 2005

Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Accumulating evidences indicates that topiramate (TPM), an antiepileptic drug with multiple mechanisms of action has neuroprotective activity. We explored the neuroprotective effect of TPM on the status epilepticus (SE)-induced hippocampal neuronal death. After development of SE by kainite injection (15 mg/Kg), rats were treated with TPM (10mg/kg) for 1 week. The neuronal death was detected by Apop tag in situ detection kit, and the expression levels of glutamate receptors were semi-quantitatively analyzed by immunoblot. Kainate-induced SE caused a significant neuronal death and cell loss in CAI and CA3 regions of hippocampus at 1 week. However, treatment of TPM for 1 week after SE markedly reduced hippocampal neuronal death. The expression of N-methyl-D-aspartate (NMDA) receptor subunit 1, was increased by SE, but was not affected by 1 week treatment of TPM. The expressions of NMDA receptor subunit 2a and 2b were not changed by either SE or TPM. As for ${\alpha}-amino-3-hydroxy-5-methyl-4-isoxazole-propionate$ (AMPA) glutamate receptors (GluR), kainate-induced SE markedly up-regulated GluR1 expression but down-regulated GluR2 expression, leading to increased formation of $Ca^{2+}$ permeable GluR2- lacking AMPA receptors. TPM administration for 1 week attenuated SE-induced expression of both the up-regulation of GluR1 and down-regulation of GluR2, reversing the ratio of GluR1/GluR2 to the control value. In conclusion, TPM protects neuronal cell death against glutamate induced excitotoxicity in kainate-induced SE model, supporting the potential of TPM as a neuroprotective agent.