This type of neuronal receptor is found throughout the nervous system.
Kainate receptors are receptors found on neurons that are activated in the presence of glutamate.
They are not well known and research, to this day, continues to try to elucidate its involvement in various disorders, especially epilepsy and diseases such as Alzheimer’s and Parkinson’s. Next we will see what is known about these peculiar ionotropic receptors.
What are kainate receptors?
Kainate receptors are found on the neuronal membrane and respond to the presence of glutamate. They were traditionally classified as non-NMDA receptors, along with the AMPA receptor.
Kainate receptors are less understood by the scientific community compared to AMPA and NMDA, which are also ionotropic receptors for the neurotransmitter glutamate.
Glutamate is known to act as the principal agent at most excitatory synapses in the central nervous system (CNS). It is a substance that mediates synaptic transmission and, when the nervous system is being formed, it participates in the processes of neuronal growth and maturation, as well as being involved in the formation and elimination of synapses, and being involved in the processes of learning and memory formation.
The receptors activated by this neurotransmitter have been divided into two families: metabotropic and ionotropic:
Metabotropics are G protein coupled and regulate the production of intracellular messengers.
The ionotropics, where the kainate receptors would be found, form a cation channel with different selectivity for certain ions, being permeable to various ions: sodium (Na +), potassium (K +) and calcium (Ca + 2).
Among the ionotropic glutamate receptors there are, as we have already mentioned, the kainate receptors, the NMDA receptors (N-methyl-D-aspartic acid) and the AMPA receptors (a-amino-3-hydroxy-5-methyl-acid). 4-isoxazolepropionic).
The postsynaptic kainate receptors are involved in excitatory neurotransmission, while the presynatic ones are involved in the inhibitory one, modulating the release of GABA through a presynaptic mechanism.
Up to five types of kainate receptor subunits are known: GluR5 (GRIK1), GluR6 (GRIK2), GluR7 (GRIK3), KA1 (GRIK4), and KA2 (GRIK5), which are similar to the AMPA and NMDA receptor subunits.
GluR subunits 5 to 7 can form homomeric channels, that is, make the receptor exclusively composed of one type of these subunits; or heteromers, meaning that there may be more than one type of subunit. The KA1 and KA2 subunits can only form functional receptors by combining with GluR subunits 5 to 7.
Molecularly speaking, ionotropic glutamate receptors are integral membrane proteins, made up of four subunits organized in a tetramer.
Kainate receptors are distributed throughout the nervous system, although their expression patterns of the subunits that make them up differ depending on the region:
1. GluR5 subunit
The GluR5 subunit is found primarily in neurons of the dorsal root ganglia, the septal nucleus, the piriformis and cingulate cortex, the subiculum, and cerebellar Purkinje cells.
2. GluR6 subunit
GluR6 is widely found in the granule cells of the cerebellum, the dentate gyrus, and the CA3 region of the hippocampus, as well as the striatum.
3. GluR7 subunit
The GluR7 subunit is sparsely found in the brain, but is expressed especially strongly in the deep cerebral cortex and striatum, as well as in inhibitory neurons in the molecular layer of the cerebellum.
4. KA1 and KA2 subunits
The KA1 subunit is found in the CA3 region of the hippocampus and has also been found in the amygdala, entorhinal cortex, and dentate gyrus. KA2 is found in all nuclei of the nervous system.
The ion channel formed by kainate receptors is permeable to sodium and potassium ions. Its conductance is similar to that of AMPA receptor channels, around 20 pS (petasiemens).
However, kainate receptors differ from AMPAs by the fact that the postsynaptic potentials generated by kainate receptors are slower than the postsynaptic potentials of AMPA receptors.
As we discussed previously, kainate receptors are involved in both presynaptic and postsynaptic action. They are found in less quantity in the brain than AMPA and NMDA receptors.
The most recent research has discovered that these types of receptors not only have an ionotropic function, directly changing the conductivity of the neuronal membrane, but that they can also involve changes at the metabotropic level, affecting the production of proteins.
It should be said that kainate is an excitotoxic substance, and it causes seizures and neuronal damage, phenomena very similar to those seen in the neurons of people suffering from epilepsy. That is why, and taking into account that all this is closely related to glutamate neurotransmission problems, research has linked problems in kainate receptors with various psychological disorders, medical problems and neurodegenerative diseases.
To date, problems in the synaptic function of kainate receptors have been linked to ischemia, hypoglycemia, epilepsy, Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, autism spectrum disorders, Huntington’s chorea and amyotrophic lateral sclerosis (ALS). Most studies have found these relationships with mutations in GluK subunits 1 through 5.
Kainate receptors play a rather modest role in synapses compared to AMPA receptors. They have a very subtle role in synaptic plasticity, affecting the probability that the postsynaptic cell will send a response to a future stimulus.
Activation of kainate receptors in the presynaptic cell can affect the amount of neurotransmitters that are released into the synaptic space. This effect can occur quickly and have effects over a long time, and repeated stimulation of kainate receptors can lead to addiction over time.
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