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Glutamate binding, activation of AMPA receptors and synaptic plasticity
Stable Identifier
R-HSA-399721
DOI
10.3180/REACT_18347.1
Type
Pathway
Species
Homo sapiens
Compartment
extracellular region
,
plasma membrane
ReviewStatus
5/5
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Neuronal System (Homo sapiens)
Transmission across Chemical Synapses (Homo sapiens)
Neurotransmitter receptors and postsynaptic signal transmission (Homo sapiens)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Homo sapiens)
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Excitatory synaptic transmission in the brain is carried out by glutamate receptors through the activation of both ionotropic and metabotropic receptors. Ionotropic glutamate receptors are of three subtypes based on distinct physiologic properties and their differential binding of exogenous ligands namely NMDA (N-methyl D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and Kainate . The ionotropic receptors are glutamate gated ion channels that initiate signaling by influx of ions, and are comprised of subunits with distinct structures and distinguished based on their agonist binding. Even though all three types of receptors are found at the glutamatergic synapses yet they exhibit great diversity in the synaptic distribution. The metabotropic glutamate receptors are a family of G-protein coupled receptors that are slow acting. Fast excitatory synaptic transmission is carried out through AMPA receptors. Post-synaptic transmission involves binding of the ligand such as glutamate/AMPA to the AMPA receptor resulting in the Na influx which causes depolarization of the membrane. NMDA receptors are blocked by Mg at resting membrane potential. NMDA receptors are activated upon coincident depolarization and glutamate binding are activated following AMPA receptor activation.NMDA receptors are blocked by Mg at resting
membrane potential. NMDA receptors are Ca permeable and their activity leads to increase in Ca which, leads to upregulation of AMPA receptors at the synapse which causes the long lasting excitatory post-synaptic potential (EPSP) which forms the basis of long term potentiation (LTP). LTP is one form of synaptic plasticity wherein the strength of the synapses is enhanced by either change in the number, increase in the efficacy by phosphorylation or change in the type of receptors. Phosphorylation of AMPA receptors changes the localization of the receptors, increases the single channel conductance, and increases the probability of open channel. GluR1 has four phosphorylation sites; serine 818 (S818) is phosphorylated by PKC and is necessary for LTP, serine 831 (S831) is phosphorylated by CaMKII that increases the delivery of receptors to the synapse and also increased their single channel conductance, threonine (T840) is implicated in LTP. Serine 845 (S845) is phosphorylated by PKA which regulates open channel probability. Long term depression is another form of plasticity wherein the number of AMPA receptors is diminished by either phosphorylation of GluR2 at Ser880 or dephosphorylation of GluR1 by protein phosphatase1, protein phosphatase 2A and protein phosphatase 2B (calcineurin).
Literature References
PubMed ID
Title
Journal
Year
16904750
Synaptic plasticity and phosphorylation
Lee, HK
Pharmacol Ther
2006
19217372
Synaptic AMPA receptor plasticity and behavior
Kessels, HW
,
Malinow, R
Neuron
2009
16713244
Regulation of Ca2+-permeable AMPA receptors: synaptic plasticity and beyond
Farrant, M
,
Cull-Candy, S
,
Kelly, L
Curr Opin Neurobiol
2006
Participants
Events
Trafficking of AMPA receptors
(Homo sapiens)
Activation of AMPA receptors
(Homo sapiens)
Participates
as an event of
Neurotransmitter receptors and postsynaptic signal transmission (Homo sapiens)
Event Information
Go Biological Process
chemical synaptic transmission (0007268)
Orthologous Events
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Bos taurus)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Caenorhabditis elegans)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Canis familiaris)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Danio rerio)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Drosophila melanogaster)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Gallus gallus)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Mus musculus)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Rattus norvegicus)
Glutamate binding, activation of AMPA receptors and synaptic plasticity (Sus scrofa)
Authored
Mahajan, SS (2008-01-14)
Reviewed
Ziff, EB (2009-05-15)
Created
Mahajan, SS (2009-03-19)
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