• The Korean Journal of Physiology and Pharmacology
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• 제5권6호
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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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• 제12권1호
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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.

• 한국안광학회지
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• 제19권3호
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• pp.413-418
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• 2014

목적: 한국관박쥐 망막의 기능을 알아보기 위해서 흥분성 신경전달물질인 글루타메이트 수용체의 분포도를 분석하였다. 방법: 성체 한국관 박쥐의 망막을 $40{\mu}m$ 수직 절편 한 후 표준면역세포화학법을 이용하였다. 면역형광이미지는 Bio-Rad MRC 1024 공초점 현미경을 사용하여 얻었다. 결과: AMPA (GluR1-4), Kainate (GluR5-7, KA1-2), NMDA (1, 2A, 2B)는 내망상층과 외망상층에 주로 분포되어 있었다. KA1은 신경절세포층에도 많은 수의 수용체가 존재하였다. 결론: 한국관박쥐는 포유류망막에 있는 신경세포와 신경전달물질을 동일하게 가지고 있었다. 한국관박쥐도 기능적 망막을 가지고 있음을 제시한다.

• Molecules and Cells
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• 제21권1호
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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.

• 생명과학회지
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• 제25권10호
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• pp.1103-1109
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• 2015

뇌 해마의 콜린성 신경분포는 학습과 기역에 연관성이 있는 것으로 알려져 있으며 이의 작용제인 carbachol 투여 시 장기기억 저하가 유도됨이 알려져 왔다. 그러나 이러한 콜린성 자극에 의한 해마 신경세포의 시냅스 내 변화기작은 완전히 알려지지 않고 있다. 본 연구에서는 아세틸콜린 수용체의 활성에 의하여 유도되는 장기기억 저하 현상에 있어 alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) 수용체가 후시냅스 표면으로부터 사라지는 현상과 이의 조절기작에 대하여 알아보고자 한다. 이를 위하여 쥐 해마의 일차세포를 추출하고 체외에서 배양한 성숙 신경세포에 carbachol 을 투여하여 장기기억 저하를 유도 하였으며, 후시냅스의 표면으로부 터 AMPA 수용체의 아단위체인 GluA2가 M1 무스카린 수용체의 길항제에 의하여 저해 되었다. 또한 콜린성 자극 에 의한 GluA2의 내재화 현상의 작용기작 연구를 위하여 쥐 해마 절편에 carbachol 투여 후 GluA2와 직접적인 상호작용을 하는 Glutam내재화 되었음을 확인하였다. 이러한 현상은 ate receptor-interacting protein 1 (GRIP1) 과 clathrine 단백질이 매개하는 세포내이입 작용을 하는 adaptin-α 단백질의 결합 변화를 관찰하였다. GluA2는 carbachol 자극에 의해 세포내이입 과정에서 adaptin-α 와의 결합이 증가하였으며 반대로 GRIP1과는 해리되었다. 이는 아세틸콜린의 수용체의 자극에 의하여 GluA2의 내제화 작용이 수반되며, 이의 작용기작으로 GluA2의 후시 냅스 표면 발현시에 결합하고 있는 GRIP1과 해리 되면서 장기기억 저하 현상이 유도됨을 의미한다.

• 동의생리병리학회지
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• 제17권4호
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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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• 제7권2호
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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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• 제20권4호
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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.

• 한국식물학회:학술대회논문집
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• 한국식물학회 2001년도 춘계학술발표대회:발표눈문요지록
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• pp.11-11
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• 2001

• 생명과학회지
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• 제15권3호
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• pp.505-512
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• 2005

신경흥분독성과 간질발작발현은 glutamate 수용체활성과 연관이 있다고 알려져 있다. a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), kainate 수용체에 대한 glutamate 활성을 포함하는 다양한 기전을 가진 항전간제인 Topiramate는 신경보호작용을 가진다는 증거가 제시되어 Topiramate가 간질발작 후 해마의 glutamate 수용체 발현에 미치는 효과를 관찰하였다. 흰쥐에 kainate를 복강 내 주사하여 간질중첩증을 유발시킨 후 Topiramate를 1주일 주사하였다 Apop tag in situ detection kit를 이용하여 세포손상을 관찰한 결과 kainate 유발 간질중첩증 1주일 후 해마의 CA1, CA3에서 심각한 세포사를 보였으나, Topiramte 처리 군에서는 세포사가 현저히 감소하였다. 간질중첩증 이후 NMDA 수용체 아형 1,2a, 2b 발현이 현저히 증가했으나 Topiramate 처치에 의해 NMDA수용체의 발현에는 뚜렷한 변화가 없었다. AMPA수용체에서는 GluR1이 간질중첩증 이후 현저히 상향 조정되었고 GluR2는 현저히 하향조정 되었다 Topiramate 1주일 처리 시 간질중첩증으로 인해 변화된 CluR1과 GluR2의 발현이 역전되었다. 결론적으로 Topiramate는 간질중침증에 의한 CluR1/CluR2 발현비의 증가로 유발되는 흥분성 신경세포사를 억제시킴으로써 신경보호작용이 있는 것으로 보인다.