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 synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

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

. 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 and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

and are key players in

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuit ...

, which is important for

learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machine learning, machines ...

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 remembered, ...

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

pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

) 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 calle ...

similarity:

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 cent ...

kainate receptors 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 dru ...

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

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

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...

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 conven ...

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. B ...

. NMDA receptors are blocked by

magnesium Magnesium is a chemical element with the 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 of the periodic ta ...

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 the flow of io ...

, 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 (Glutamate receptor 2, or GluR-2) is a protein that in humans is encoded by the ''GRIA2'' (or ''GLUR2'') gene and it is a subunit found in the AMPA receptors. Function Glutamate receptors are ...

; 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 t ...

; 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 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 rec ...

; 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-ga ...

; 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 heterome ...

; 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 ioni ...

; 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; 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 a ...

; GluN2C/ GRIN2C; GluN2D/ GRIN2D; GluN3A/

GRIN3A Glutamate

MDA MDA, mda, or ''variation'', may refer to: Places * Moldova, a country in Europe with the ISO 3166-1 country code MDA Politics * Meghalaya Democratic Alliance (2018), ruling coalition government in the Indian State of Meghalaya led by National Pe ...

receptor subunit 3A is a protein that in humans is encoded by the ''GRIN3A'' gene. Function This gene encodes a subunit of the N-methyl-D-aspartate (NMDAR) receptors, which belong to the superfamily of glutamate receptor, glut ...

; GluN3B/

GRIN3B Glutamate MDAreceptor subunit 3B is a protein that in humans is encoded by the ''GRIN3B'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''genera ...

;

References

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