Kainate receptor
Encyclopedia
NMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...
ionotropic receptors which respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from red algae
Algae
Algae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...
Digenea simplex. KARs are less well understood than AMPA
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
and NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
s, the other ionotropic glutamate receptor
Ionotropic glutamate receptor
The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory. There are three classes of ionotropic glutamate receptor, namely NMDA , AMPA and kainate receptors...
s. Kainate postsynaptic receptors are involved in excitatory neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
. Presynaptic kainate receptors have been implicated in inhibitory neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
by modulating release of the inhibitory neurotransmitter GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
through a presynaptic mechanism.
Structure
There are five types of kainate receptor subunits, GluR5GRIK1
Glutamate receptor, ionotropic, kainate 1, also known as GRIK1, is a protein that in humans is encoded by the GRIK1 gene.- Function :...
, GluR6
GRIK2
Glutamate receptor, ionotropic kainate 2 is a protein that in humans is encoded by the GRIK2 gene.- Clinical significance :Homozygosity for a GRIK2 deletion-inversion mutation is associated with nonsyndromic autosomal recessive mental retardation....
, GluR7
GRIK3
Glutamate receptor, ionotropic kainate 3 is a protein that in humans is encoded by the GRIK3 gene....
, KA1
GRIK4
GRIK4 is a kainate receptor subtype belonging to the family of ligand-gated ion channels which is encoded by the gene.-Function:...
and KA2
GRIK5
Glutamate receptor, ionotropic kainate 5 is a protein that in humans is encoded by the GRIK5 gene.-Interactions:GRIK5 has been shown to interact with DLG4 and GRIK2....
, which are similar to AMPA and NMDA receptor subunits and can be arranged in different ways to form a tetramer, a four subunit receptor. GluR5-7 can form homomers (ex. a receptor composed entirely of GluR5) and heteromers (ex. a receptor composed of both GluR5 and GluR6), however, KA1 and KA2 can only form functional receptors by combining with one of the GluR5-7 subunits.
Each KAR subunit begins with a 400 residue extracellular N-terminal domain, which plays a key role in assembly, followed by the 1st segment of the neurotransmitter binding cleft called S1. This segment then passes through the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
, forming the first of three membrane spanning regions called M1. The M2 segment then begins on the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic face of the membrane, pushes into the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
about half way, and then dips back out to the cytoplasm. This segment has been termed the "p loop", and as is the case of closely related AMPA
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
receptors, determines the calcium permeability of the receptor. M2 turns into M3, another transmembrane spanning segment which emerges on the extracellular face to complete the neurotransmitter binding site (a portion called S2). M4 begins extracellularly, and passes again through the membrane into the cytoplasm, forming the C-terminal of the protein.
Conductance
The ion channelIon channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
formed by kainate receptors is permeable to sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
and potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
ions. The amount of sodium and potassium the channels allow through their pores per second (their conductance) is similar to that of AMPA channels, at about 20 pS
Siemens (unit)
The siemens is the SI derived unit of electric conductance and electric admittance. Conductance and admittance are the reciprocals of resistance and impedance respectively, hence one siemens is equal to the reciprocal of one ohm, and is sometimes referred to as the mho. In English, the term...
. However, the openings of KARs are much shorter in duration than AMPA openings. Their permeability to Ca++ is usually very slight but varies with subunits and RNA editing at the tip of the p loop.
Roles
Kainate receptors play a role in both pre- and postsynaptic neurons. They have a somewhat more limited distribution in the brainBrain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
compared to AMPA and NMDA receptors, and their function is not well defined.
The role of KARs in sensory transduction has been connected to epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
.
Plasticity
Unlike AMPA receptors, kainate receptors play only a minor role in signaling at synapseSynapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
s.
Rather, kainate receptors may have a more subtle role in synaptic plasticity
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...
, affecting the likelihood that the postsynaptic cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
will fire in response to future stimulation. Activating kainate receptors in the presynaptic cell can affect the amount of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s that are released This effect may occur quickly and last for a long time, and the effects of repetitive stimulation of KARs can be additive over time..
Antagonists
- CNQXCNQXCNQX is a competitive AMPA/kainate receptor antagonist. Its chemical formula is C9H4N4O4.-External links:**...
- DNQXDNQXDNQX is an AMPA and Kainate receptor antagonist. It is used in a variety of molecular biology subfields, notably neurophysiology, to assist researchers in determining the properties of various types of ion channels....
- NS102NS102NS102 is a kainate receptor ligand....
- Selective of Kainate receptor over AMPA receptorAMPA receptorThe α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA... - Kynurenic acidKynurenic acidKynurenic acid is a product of the normal metabolism of amino acid L-tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an antagonist at excitatory amino acid receptors...
- endogenous ligand - TezampanelTezampanelTezampanel is a drug originally developed by Eli Lilly which acts as an antagonist at the AMPA and kainate families of ionotropic glutamate receptors, with selectivity for the GluR5 subtype of the kainate receptor. It has neuroprotective and anticonvulsant effects...