Kainate receptors: what are they and what are their functions?

This type of neuronal receptor is distributed throughout the nervous system.

The kainate receptors are receptors found in neurons that are activated in the presence of glutamate.

They are not very well known and research is still trying to elucidate their involvement in various disorders, especially epilepsy and diseases such as Alzheimer's and Parkinson's disease. Below we will see what is known about these peculiar ionotropic receptors.

What are kainate receptors?

The kainate receptors are found in the neuronal membrane and respond to the presence of glutamate.. Traditionally they were classified as non-NMDA receptors, together with the AMPA receptor.

The 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 a major player at most excitatory synapses in the central nervous system (CNS). of the central nervous system (CNS). It is a substance that mediates synaptic transmission and, when the nervous system is being formed, participates in the processes of neuronal growth and maturation, as well as being involved in the formation and elimination of synapses, and is involved in the processes of learning and memory formation.

The receptors activated by this neurotransmitter have been divided into two families: metabotropic and ionotropic receptors:

Metabotropic ones are coupled to G proteins and regulate the production of intracellular messengers..

Ionotropic receptors, where kainate receptors would be found, form a cation channel with different selectivity for certain ions, being permeable to several ionsbeing permeable to several ions: sodium (Na+), potassium (K+) and calcium (Ca+2).

Among the ionotropic glutamate receptors are, as we have already mentioned, kainate receptors, NMDA receptors (N-methyl-D-aspartic acid) and AMPA receptors (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).

Postsynaptic kainate receptors are involved in excitatory neurotransmission, whereas presynaptic kainate receptors are involved in inhibitory neurotransmission, modulating GABA release via a presynaptic mechanism.

Structure

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 subunits of AMPA and NMDA receptors.

GluR subunits 5 to 7 can form homomeric channels.The KA1 and KA2 subunits can only form functional receptors by combining with GluR subunits 5 to 7, i.e., making the receptor exclusively composed of one type of these subunits; or heteromers, making it possible to have more than one type of subunit. 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. are integral membrane proteins, consisting of four subunits arranged in a tetramer..

Distribution

Kainate receptors are distributed throughout the nervous system, although their expression patterns of the subunits that comprise them differ according to the region:

1. GluR5 subunit

The GluR5 subunit is found mainly in neurons of the dorsal root ganglia. dorsal root ganglia, septal nucleus, piriform and cingulate cortex, subiculum and Purkinje cells. cerebellar neurons.

2. GluR6 subunit

GluR6 is widely found in the granular cells of the cerebellum, the dentate gyrus and the CA3 region of the hippocampus, as well as in the striatum.as well as in the striatum.

3. GluR7 subunit

The GluR7 subunit is found sparsely in the brain, but is expressed, especially strongly, in the deep cerebral cortex and striatum, as well as in the inhibitory neurons of 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..

Conductance

The ion channel formed by kainate receptors is permeable to sodium and potassium ions. Its conductance is similar to that of the AMPA receptor channels of about 20 pS (petasiemens).

However, kainate receptors differ from AMPA receptors in that the postsynaptic potentials generated by kainate receptors are slower than the postsynaptic potentials of AMPA receptors.

Synaptic function

As previously mentioned, the kainate receptors are involved in both presynaptic action receptors are involved in both presynaptic and postsynaptic action.. They are found in smaller quantities in the brain than AMPA and NMDA receptors.

More recent research has found that these types of receptors not only have an ionotropic function, directly changing neuronal membrane conductance, but, in addition, may also involve changes at the metabotropic level, affecting the production of proteins.

It should be said that kainate is an excitotoxic substance, and 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 several psychological disorders, medical problems and neurodegenerative diseases.

To date, problems in the synaptic function of kainate receptors have been linked with ischemia, hypoglycemia, epilepsy, Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, bipolar disorders, neurodegenerative disorders, and other neurodegenerative diseases.Most studies have found these relationships with mutations in GluK subunits 1 through 5.

Neuronal plasticity

Kainate receptors play a rather modest role at 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 on the presynaptic cell can affect the amount of neurotransmitters that will be released into the synaptic space. to be released into the synaptic space. This effect can occur rapidly and have effects over a long time, and repeated stimulation of kainate receptors can lead to addiction over time.

Bibliographic references:

• Dingledine R, Borges K, Bowie D, Traynelis SF (March 1999). "The glutamate receptor ion channels". Pharmacological Reviews. 51 (1): 7-61. PMID 10049997. Archived from the original (abstract) on 2009-02-13. Retrieved 2007-12-28.
• Huettner JE (August 2003). "Kainate receptors and synaptic transmission". Progress in Neurobiology. 70 (5): 387–407. doi:10.1016/S0301-0082(03)00122-9
• Contractor A, Mulle C, Swanson GT (March 2011). "Kainate receptors coming of age: milestones of two decades of research". Trends in Neurosciences. 34 (3): 154–63. doi:10.1016/j.tins.2010.12.002
• Fritsch B, Reis J, Gasior M, Kaminski RM, Rogawski MA (April 2014). "Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis". The Journal of Neuroscience. 34 (17): 5765–75.
• Rodriguez-Moreno, Antonio. (2003). Kainate receptors. Their function in the regulation of GABAergic synaptic transmission in the hippocampus. Revista de neurologia. 36. 852-9.