Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitral cell of the olfactory bulb is the primary relay neuron that transmits information from the olfactory receptors to the rest of the brain. This excitatory neuron releases glutamate from presynaptic dendrites and axon terminals. All rat mitral cells studied showed strong, selective, and widespread metabotropic glutamate receptor mGluR1 alpha immunoreactivity on the presynaptic membrane of dendrites, often at the synaptic vesicle release site, when examined with light and electron microscopy. The finding of glutamate receptors on mitral cell secondary dendrites supports the conclusion that not all dendritic membrane with glutamate receptors necessarily have gray type I asymmetrical synaptic specializations. In contrast, the metabotropic glutamate receptor mGluR5 was not found in mitral cells but was expressed by granule cells and astrocytes around mitral dendrites. Both mGluR1 alpha and mGluR5 were expressed early in development, with strong immunostaining present by postnatal day 1. MGluR1 alpha staining at birth mirrored the adult staining pattern. MGluR5 staining at birth showed different patterns of immunostaining than that found in the adult, particularly in the external plexiform layer. In vitro olfactory bulb neurons and their dendrites from embryonic day (E) 18 olfactory bulbs responded to t-ACPD and quisqualate, selective and nonselective metabotropic glutamate receptor agonists, and to several ionotropic glutamate agonists with increases in intracellular Ca2+ as studied with fura-2 digital imaging. These data indicate that the receptors were functionally active at an early stage of development. Application of the glutamate receptor blockers d-2-amino-5-phosphonovalerate (AP5) and 6-cyano-7-nitroquinoxaline (CNQX) to E17 olfactory bulb neurons after only 4 days in vitro resulted in a dramatic decrease in Ca2+ levels in 70% of 128 cells tested, suggesting that embryonic neurons after a short time in vitro can actively secrete glutamate. The presence of glutamate receptors on the long mitral cell dendrite suggests that it would be able to respond to release of its own excitatory transmitter, probably at an early stage of development. In the probable absence of other excitatory input to the secondary mitral dendrites, it would be the only excitatory "input." This autoexcitatory response would be modulated by release of GABA from olfactory interneurons occurring milliseconds after glutamate release induced by olfactory nerve activation. This novel type of neuronal microcircuitry would potentially amplify signal transmission and current spread along the long mitral dendrites and could play an important role in lateral inhibition of olfactory neurons.
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PMID:Presynaptic metabotropic glutamate receptors in adult and developing neurons: autoexcitation in the olfactory bulb. 749 28

NMDA receptors are composed of multiple receptor subunit proteins, of which NMDAR1 appears to be a critical component for normal receptor function (Nakanishi, 1992). In this study, quantitative immunocytochemical methods were used at the light and electron microscopic levels to localize NMDAR1 subunits in the primary motor (M1) and somatic sensory (S1) cortex of monkeys, and in the primary visual cortices (V1) of monkey and human. Three principal features of NMDAR1 subunit organization were examined in detail in the monkey cortex: (1) the laminar and cellular distribution patterns, relying in part on double-labeling paradigms with the calcium-binding proteins parvalbumin (PV) and calretinin (CR) as markers for discrete subpopulations of GABAergic interneurons; (2) the codistribution of NMDAR1 subunits with non-NMDA ionotropic receptor subunits; (3) a quantitative assessment of the percentages of asymmetrical synapses in layers II/III, IV, and V/VI that were NMDAR1 immunoreactive. In monkey M1, S1, and V1, NMDAR 1 immunoreactivity was present in all layers, localized primarily to large numbers of pyramidal cell somata and proximal apical dendrites, to presumptive spiny stellate cells in layer IV of V1, and to the vast majority (approximately 80-90%) of PV-immunoreactive cells. By contrast, NMDAR1 immunoreactivity was present in only a very small percentage of the CR-immunoreactive cells (approximately 6-9%). Colocalization with non-NMDA receptor subunits showed that all cells (100%) that contained GluR2/3 subunits were also NMDAR1 immunoreactive. In addition, the complete codistribution of GluR5/6/7 subunits with GluR2/3 subunits suggests, indirectly, that all GluR5/6/7-immunoreactive cells are also NMDAR1 immunoreactive. The laminar and cellular distribution patterns of immunostaining in human V1 were very similar to those in monkey V1. Electron microscopy of monkey sections confirmed an extensive dendritic and synaptic localization of NMDAR1 subunits. Labeling of synapses was present on asymmetrical postsynaptic densities associated with both dendritic shafts and spines. In supragranular layers of V1, a greater percentage of asymmetrical synapses were NMDAR1 immunopositive (44%) in comparison to layer IVC beta (34%) or deep layers (19%). In contrast, in area 3b of S1, the percentage of labeled synapses was greatest in layer IV (45%) in comparison to superficial (26%) and deep (37%) layers, while in M1, the percentages of labeled synapses were similar between superficial (46%) and deep (40%) layers. Taken together, these data indicate that NMDAR1-immunoreactive cells in neocortex represent a morphologically, functionally, and neurochemically heterogeneous population.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Distribution and synaptic localization of immunocytochemically identified NMDA receptor subunit proteins in sensory-motor and visual cortices of monkey and human. 820 75

Trans-1-amino-cyclopentyl-1,3-dicarboxylic acid (trans-ACPD), a specific agonist of the glutamate phosphoinositide-coupled receptor (Qp receptor), increased the amplitude of the outward K+ current recorded in the whole-cell configuration of the patch-clamp technique in mouse cultured cerebellar granule cells. This effect was abolished by buffering internal Ca2+ with BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid]. Activation of a large-conductance K+ channel was observed when trans-ACPD or quisqualic acid (QA), another Qp receptor agonist, was applied outside the cell-attached patch pipettes. No activation was observed with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), a specific agonist of ionotropic non-N-methyl-d-aspartate (non-NMDA) receptors. The effects of trans-ACPD or QA were potentiated in the presence of external Ca2+. The channel was also directly activated by both micromolar concentrations of internal Ca2+ and membrane depolarization. Its unitary conductance was 100 - 115 pS under asymmetrical K+ and 195 - 235 pS under high symmetrical K+ conditions. In the absence of agonist, the channel was blocked by 1 mM external tetraethylammonium. This is the first description of a large conductance Ca2+-activated K+ channel in cultured cerebellar granule cells. It possesses properties similar to those of the so-called 'big K+ channel' described in other preparations. Our cell-attached experiments demonstrated an indirect coupling between Qp receptors and this channel. The most likely hypothesis is that the second messenger system inositol 1,4,5-triphosphate (IP3)-Ca2+ was involved in the coupling process. This hypothesis was further strengthened by our whole-cell experiments. On the basis of the voltage- and Ca2+-sensitivities of the studied channel, we estimated an increase of 350 to 570 nM in internal Ca2+ concentration when Qp receptors were stimulated by 100 microM trans-ACPD. Under physiological conditions, stimulation of Qp receptors by the endogenous neurotransmitter should lead to similar K+ channel activation and therefore would tend to reduce the efficacy of ionotropic glutamate synaptic receptor stimulation responsible for cell excitation.
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PMID:Activation of a Large-conductance Ca2+-Dependent K+ Channel by Stimulation of Glutamate Phosphoinositide-coupled Receptors in Cultured Cerebellar Granule Cells. 1210 64

Fast excitatory synaptic responses in basolateral amygdala (BLA) neurons are mainly mediated by ionotropic glutamate receptors of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype. AMPA receptors containing an edited GluR2 subunit are calcium impermeable, whereas those that lack this subunit are calcium permeable and also inwardly rectifying. Here, we sought to determine the extent to which synapses in the rat BLA have AMPA receptors with GluR2 subunits. We assessed GluR2 protein expression in the BLA by immunocytochemistry with a GluR2 subunit-specific antiserum at the light and electron microscopic level; for comparison, a parallel examination was carried out in the hippocampus. We also recorded from amygdala brain slices to examine the voltage-dependent properties of AMPA receptor- mediated evoked synaptic currents in BLA principal neurons. At the light microscopic level, GluR2 immunoreactivity was localized to the perikarya and proximal dendrites of BLA neurons; dense labeling was also present over the pyramidal cell layer of hippocampal subfields CA1 and CA3. In electron micrographs from the BLA, most of the synapses were asymmetrical with pronounced postsynaptic densities (PSD). They contained clear, spherical vesicles apposed to the PSD and were predominantly onto spines (86%), indicating that they are mainly with BLA principal neurons. Only 11% of morphological synapses in the BLA were onto postsynaptic elements that showed GluR2 immunoreactivity, in contrast to hippocampal subfields CA1 and CA3 in which 76% and 71% of postsynaptic elements were labeled (p < 0.001). Synaptic staining in the BLA and hippocampus, when it occurred, was exclusively postsynaptic, and particularly heavy over the PSD. In whole-cell voltage clamp recordings, 72% of BLA principal neurons exhibited AMPA receptor-mediated synaptic currents evoked by external capsule stimulation that were inwardly rectifying. Although BLA principal neurons express perikaryal and proximal dendritic GluR2 immunoreactivity, few synapses onto these neurons express GluR2, and a preponderance of principal neurons have inwardly rectifying AMPA-mediated synaptic currents, suggesting that targeting of GluR2 to synapses is restricted. Many BLA synaptic AMPA receptors are likely to be calcium permeable and could play roles in synaptic plasticity, epileptogenesis and excitoxicity.
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PMID:Evidence for low GluR2 AMPA receptor subunit expression at synapses in the rat basolateral amygdala. 1604 45