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IGluR
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players in synaptic plasticity, which is important for learning and memory. iGluRs have been divided into four subtypes on the basis of their ligand binding properties (pharmacology) and sequence similarity: AMPA receptors, kainate receptors, NMDA receptors and delta receptors (see below). AMPA receptors are the main charge carriers during basal transmission, permitting influx of sodium ions to depolarise the postsynaptic membrane. NMDA receptors are blocked by magnesium ions and therefore only permit ion flux following prior depolarisation. This enables them to act as coincidence detectors for synaptic plasticity. Calcium influx through NMDA receptors leads to persistent modifications in the strength of synaptic transmission. iGluRs are tetr ...
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AMPA Receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synaptic transmission in the central nervous system (CNS). It has been traditionally classified as a non-NMDA_receptor, NMDA-type receptor, along with the kainate receptor. Its name is derived from its ability to be activated by the artificial glutamate analog AMPA. The receptor was first named the "quisqualate receptor" by Watkins and colleagues after a naturally occurring agonist quisqualic acid, quisqualate and was only later given the label "AMPA receptor" after the selective agonist developed by Tage Honore and colleagues at the Royal Danish School of Pharmacy in Copenhagen. The ''GRIA2''-encoded AMPA receptor ligand binding core (GluA2 LBD) was the first glutamate receptor ion channel domain to be protein crystal, crystallized. Structure ...
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AMPA Receptors
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate ( iGluR) that mediates fast synaptic transmission in the central nervous system (CNS). It has been traditionally classified as a non-NMDA-type receptor, along with the kainate receptor. Its name is derived from its ability to be activated by the artificial glutamate analog AMPA. The receptor was first named the "quisqualate receptor" by Watkins and colleagues after a naturally occurring agonist quisqualate and was only later given the label "AMPA receptor" after the selective agonist developed by Tage Honore and colleagues at the Royal Danish School of Pharmacy in Copenhagen. The ''GRIA2''-encoded AMPA receptor ligand binding core (GluA2 LBD) was the first glutamate receptor ion channel domain to be crystallized. Structure and function Subunit composition AMPARs are composed of four types of subun ...
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GRID2
Glutamate receptor, ionotropic, delta 2, also known as GluD2, GluRδ2, or δ2, is a protein that in humans is encoded by the ''GRID2'' gene. This protein together with GRID1, GluD1 belongs to the delta receptor subtype of ionotropic glutamate receptors. They possess 14–24% DNA sequence, sequence homology (biology), homology with AMPA receptor, AMPA, Kainate receptor, kainate, and NMDA receptor, NMDA subunits, but, despite their name, do not actually bind glutamate or various other glutamate agonists. delta iGluRs have long been considered orphan receptors as their endogenous ligand was unknown. They are now believed to bind glycine and D-serine but these do not result in channel opening. Function GluD2-containing receptors are selectively/predominantly expressed in Purkinje cells in the cerebellum where they play a key role in synaptogenesis, synaptic plasticity, and motor coordination. GluD2 induces synaptogenesis through interaction of its N-terminal domain with Cbln1, wh ...
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Ligand-gated Ion Channels
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter. When a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft. The neurotransmitter then binds to receptors located on the postsynaptic neuron. If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either a depolarization, for an excitatory receptor response, or a hyperpolarization, for an inhibitory response. These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain wh ...
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Coincidence Detection In Neurobiology
Coincidence detection in the context of neurobiology is a process by which a neuron or a neural circuit can encode information by detecting the occurrence of temporally close but spatially distributed input signals. Coincidence detectors influence neuronal information processing by reducing temporal jitter, reducing spontaneous activity, and forming associations between separate neural events. This concept has led to a greater understanding of neural processes and the formation of computational maps in the brain. Principles of coincidence detection Coincidence detection relies on separate inputs converging on a common target. Consider a basic neural circuit with two input neurons, A and B, that have excitatory synaptic terminals converging on a single output neuron, C (Fig. 1). If each input neuron's EPSP is subthreshold for an action potential at C, then C will not fire unless the two inputs from A and B are temporally close together. Synchronous arrival of these two inputs m ...
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GRIK4
GRIK4 (''glutamate receptor, ionotropic, kainate 4'') is a kainate receptor subtype belonging to the family of ligand-gated ion channels which is encoded by the gene. Function This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Clinical significance A single nucleotide polymorphism ( rs1954787) in the GRIK4 gene has shown a treatment-response-association with antidepressant treatment. Variation in GRIK4 have been associated with both increased and decreased risk of bipolar disorder. A possible mechanism for this observation is that the sequence variation influences secondary structures in the 3' UTR. Interfer ...
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GRIK3
Glutamate receptor, ionotropic kainate 3 is a protein that in humans is encoded by the ''GRIK3'' gene. This gene encodes a protein that belongs to the ligand-gated ionic channel family. It can coassemble with either GRIK4 or GRIK5 to form heteromeric receptors and acts as an excitatory neurotransmitter at many synapses in the central nervous system. RNA editing in the mRNA has been reported. See also * Kainate receptor Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug ... References Further reading * * * * * * * * * * * * External links * Ionotropic glutamate receptors {{membrane-protein-stub ...
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GRIK2
Glutamate ionotropic receptor kainate type subunit 2, also known as ionotropic glutamate receptor 6 or GluR6, is a protein that in humans is encoded by the ''GRIK2'' (or ''GLUR6'') gene. Function This gene encodes a subunit of a kainate glutamate receptor. This receptor may have a role in synaptic plasticity, learning, and memory. It also may be involved in the transmission of visual information from the retina to the hypothalamus. The structure and function of the encoded protein is influenced by RNA editing. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene. Clinical significance Homozygosity for a GRIK2 deletion-inversion mutation is associated with non-syndromic autosomal recessive mental retardation. Interactions GRIK2 has been shown to interact with: * DLG1, * DLG4, * GRID2, * GRIK5, * GRIP1, * PICK1 and * SDCBP. RNA Editing Pre-mRNA for several neurotransmitter receptors and ion channels are substrates ...
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GRIK1
Glutamate receptor, ionotropic, kainate 1, also known as GRIK1, is a protein that in humans is encoded by the ''GRIK1'' gene. Function This gene encodes one of the many ionotropic glutamate receptor (GluR) subunits that function as a ligand-gated ion channel. The specific GluR subunit encoded by this gene is of the kainate receptor subtype. Receptor assembly and intracellular trafficking of ionotropic glutamate receptors are regulated by RNA editing and alternative splicing. These receptors mediate excitatory neurotransmission and are critical for normal synaptic function. Two alternatively spliced transcript variants that encode different isoforms have been described. Exons of this gene are interspersed with exons from the C21orf41 gene, which is transcribed in the same orientation as this gene but does not seem to encode a protein. Interactions GRIK1 has been shown to interact with DLG4, PICK1 and SDCBP. RNA editing Type A to I RNA editing is catalyzed by a family of a ...
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GRID1
Glutamate receptor delta-1 subunit also known as GluD1 or GluRδ1 is a transmembrane protein (1009 aa) encoded by the ''GRID1'' gene. A C-terminal GluD1 splicing isoform (896 aa) has been described based on mRNA analysis. Function This gene encodes a subunit of glutamate receptor ligand-gated ion channel. Most of these channels mediate fast excitatory synaptic transmission in the central nervous system. GluD1 is expressed in the central nervous system and is important in synaptic plasticity. Clinical significance Several genetic epidemiology studies have shown a strong association between several variants of the ''GRID1'' gene and increased risk of developing schizophrenia. See also * ''GRID2 Glutamate receptor, ionotropic, delta 2, also known as GluD2, GluRδ2, or δ2, is a protein that in humans is encoded by the ''GRID2'' gene. This protein together with GluD1 belongs to the delta receptor subtype of ionotropic glutamate receptors. ...'' References Further ...
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GRIA4
Glutamate receptor 4 is a protein that in humans is encoded by the ''GRIA4'' gene. This gene is a member of a family of L-glutamate-gated ion channels that mediate fast synaptic excitatory neurotransmission. These channels are also responsive to the glutamate agonist, alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA). Some haplotypes of this gene show a positive association with schizophrenia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Like the other AMPA receptor subunits, GluA4 occurs as flip and flop spliced variant. In addition, GluA4 CTD long and short isoforms exist, and presumably an ATD-only isoform (433 aa). Interactions GRIA4 has been shown to interact with CACNG2, GRIP1, PICK1 and PRKCG. RNA editing Several ion channels and neurotransmitters receptors pre-mRNa are substrates for ADARs. This includes 5 subunits of the glutamate receptor ionotropic AMPA glutamate receptor subunits (Glur2, Glur3, Glur4 ...
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GRIA3
Glutamate receptor 3 is a protein that in humans is encoded by the ''GRIA3'' gene. Function Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. This gene belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Alternative splicing at this locus results in several different isoforms which may vary in their signal transduction properties. Genome studies have uncovered a tentative link between defective GRIA3 variants and a highly elevated risk of schizophrenia. Interactions GRIA3 has been shown to interact with GRIP1 and PICK1. RNA editing Several ion ch ...
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