Ionotropic glutamate receptors (iGluRs) are

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 res ...

that are activated by the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

. They mediate the majority of excitatory synaptic transmission throughout the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

and are key players in

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to Chemical synapse#Synaptic strength, strengthen or weaken over time, in response to increases or decreases in their activity. Since memory, memories are postulated to be represent ...

, which is important for

learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, Attitude (psychology), attitudes, and preferences. The ability to learn is possessed by humans, non-human animals, and ...

and

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...

. iGluRs have been divided into four subtypes on the basis of their ligand binding properties (

pharmacology Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...

) and

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...

similarity:

AMPA receptors The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitator ...

kainate receptors Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate (neurotransmitter), glutamate. They were first identified as a distinct receptor type through their selective activation ...

NMDA receptors The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the othe ...

and delta receptors (see below). AMPA receptors are the main charge carriers during basal transmission, permitting influx of

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

ions An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

to depolarise the postsynaptic

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

. NMDA receptors are blocked by

magnesium Magnesium is a chemical element; it has Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 ...

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 Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron) ...

. iGluRs are tetramers (they are formed of four subunits). All subunits have a shared architecture with four domain layers: two extracellular clamshell domains called the N-terminal domain (NTD) and ligand-binding domain (LBD; which binds glutamate), the transmembrane domain (TMD) that forms the

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

, and an intracellular C-terminal domain (CTD).

Human proteins/genes encoding iGluR subunits

: GluA1/

GRIA1 Glutamate receptor 1 is a protein that in humans is encoded by the ''GRIA1'' gene. Function Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophys ...

; GluA2/

GRIA2 Glutamate ionotropic receptor AMPA type subunit 2 (also known as glutamate receptor 2 or GluR-2) is a protein in humans that is encoded by the ''GRIA2'' (also called ''GLUR2'') gene. It functions as a subunit of AMPA receptors. Function Glut ...

; GluA3/

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 neurophys ...

; GluA4/

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 ...

; delta receptors: GluD1/

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 ...

; GluD2/ GRID2; kainate receptors: GluK1/

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-g ...

; GluK2/

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 glut ...

; GluK3/

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 hetero ...

; GluK4/

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 ion ...

; GluK5/

GRIK5 Glutamate receptor, ionotropic kainate 5 is a protein that in humans is encoded by the ''GRIK5'' gene. Function This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory ...

;

: GluN1/

GRIN1 Glutamate MDAreceptor subunit zeta-1 is a protein that in humans is encoded by the ''GRIN1'' gene. The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily w ...

; GluN2A/

GRIN2A Glutamate MDAreceptor subunit epsilon-1 is a protein that in humans is encoded by the ''GRIN2A'' gene. With 1464 amino acids, the canonical GluN2A subunit isoform is large. GluN2A-short isoforms specific to primates can be produced by alternative ...

; GluN2B/

GRIN2B Glutamate MDAreceptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the ''GRIN2B'' gene. NMDA receptors ''N''-methyl-D-aspartate (NMDA) receptors are ...

; GluN2C/

GRIN2C Glutamate MDAreceptor subunit epsilon-3 is a protein that in humans is encoded by the ''GRIN2C'' gene. Function N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved i ...

; GluN2D/

GRIN2D Glutamate MDAreceptor subunit epsilon-4 is a protein that in humans is encoded by the ''GRIN2D'' gene. Function N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved ...

; GluN3A/ GRIN3A; GluN3B/ GRIN3B;

References

Protein domains Protein families Membrane proteins Ionotropic glutamate receptors {{membrane-protein-stub