Abstract
On this planet, the mammalian brain is probably the most complex cellular network. In this system, glutamate is the dominant neurotransmitter, and it mediates the fast communication between the units of the network. Glutamate’s main sites of fast action are the ionotropic glutamate receptors (iGluRs). The iGluRs are a group of receptors that are related in their amino acid sequences and belong to the superfamily of ion channels containing a P-loop as an ion pore. These P-loop channels consist of several subunits. In the case of iGluRs, this subunit assembly is tetrameric. Most iGluRs are associated with auxiliary proteins. The auxiliary proteins can be involved in surface delivery and trafficking of the iGluR, but they can also modulate iGluR channel properties.
The iGluR family consists of four subgroups: AMPA, NMDA, kainate, and orphan receptors, distinguished by their pharmacological profile. The AMPA receptors are directly responsible for the fast signal transmission at synapses, which represents the communication points between the individual neurons. In contrast, the NMDA receptors do not directly participate in fast synaptic transmission; instead, they are the most fundamental modulators of the strength of the synaptic AMPA receptor currents during development and in the mature brain. Together with the AMPA receptors, NMDA receptors keep synapses flexible and thus permit a continuous incorporation or removal of new information into and from the network; in other words, they are necessary for the formation and the extinction of memory. This simple picture of iGluR-mediated neurotransmission is, however, likely to be substantially modified in the future, in view of the great complexity of the iGluR system and its involvement in neurological and neuropsychiatric disorders.
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Abbreviations
- 3D:
-
Three dimensional
- ADAR:
-
Adenosine deaminase acting on RNA
- AMPA:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- ASD:
-
Autism spectrum disorder
- CA1:
-
Cornu Ammonis region 1
- CA3:
-
Cornu Ammonis region 3
- CaMKII:
-
Calmodulin-dependent protein kinase type II
- cDNA:
-
mRNA complementary DNA
- C. elegans :
-
Caenorhabditis elegans
- CKAMP:
-
Cystine-knot AMPA receptor modulating protein
- CNIH:
-
Cornichon homologs
- CNS:
-
Central nervous system
- CUB:
-
Complement C1r/C1s protein domain
- D-AP5:
-
(2R)-Amino-5-phosphonovaleric acid (also known as APV)
- DG:
-
Dentate gyrus
- GABA:
-
(γ-aminobutyric acid)
- GAD:
-
Glutamate decarboxylase
- Gi:
-
Guanine nucleotide-binding protein for inhibiting activating the cAMP-dependent pathway
- GKAP:
-
Guanylate kinase-associated protein
- Gs:
-
Guanine nucleotide-binding protein for activating the cAMP-dependent pathway
- GRIP:
-
Glutamate receptor interacting protein
- ID:
-
Intellectual Disability
- iGluRs:
-
Ionotropic glutamate receptors
- IUPHAR:
-
International Union of Basic and Clinical Pharmacology
- KscA:
-
Potassium channel from Streptomyces lividans
- LBD:
-
Ligand-binding domain
- LGICs:
-
Ligand-gated ion channels
- LTD:
-
Long-term depression
- LTP:
-
Long-term potentiation
- MAGUK:
-
Membrane-associated guanylate kinase
- mGluRs:
-
Metabotropic glutamate receptors
- MWM:
-
Morris water maze
- n-AChR:
-
Nicotinic acetylcholine receptor
- NDE:
-
Near-death experience
- NETO:
-
Neuropilin tolloid-like 1
- NMDA:
-
N-methyl-D-aspartate
- PNDD:
-
Psychiatric and neurodevelopmental disorders
- PhD:
-
Philosophiae doctor
- PKCα:
-
Protein kinase Cα
- PICK1:
-
Protein interacting with C kinase 1
- pre-mRNA:
-
Premature messenger RNA
- PSD:
-
Postsynaptic density
- PSD95:
-
Postsynaptic density proteins 95
- SAP97:
-
Synapse-associated protein 97
- SCZ:
-
Schizophrenia
- SHANK:
-
SH3 and multiple ankyrin repeat domain proteins
- SRM:
-
Spatial reference memory
- SWM:
-
Spatial working memory
- SOL:
-
Suppressor of Lurcher
- Syngap:
-
Synaptic ras GTPase-activating protein
- TARP:
-
Transmembrane AMPA receptor regulatory proteins
- TM:
-
Transmembrane spanning
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Sprengel, R., Eltokhi, A. (2022). Ionotropic Glutamate Receptors (and Their Role in Health and Disease). In: Pfaff, D.W., Volkow, N.D., Rubenstein, J. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6434-1_4-3
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