Kainate receptors: what are they and what are their functions

Kainate receptors They are receptors found in neurons that are activated in the presence of glutamate.

They are not very well known and research, to this day, continues trying to elucidate what implication has in various disorders, especially epilepsy and diseases such as Alzheimer's and Parkinson. Next we will see what is known about these peculiar ionotropic receptors.

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What are kainate receptors?

Kainate receptors They are found in the neuronal membrane and respond to the presence of glutamate.. Traditionally they were 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 primary agent at most excitatory synapses. 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 growth and neuronal maturation, in addition to being involved in the formation and elimination of synapses, and being involved in the learning processes and formation of the memory.

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

Metabotropics are coupled to G proteins 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 several ions: sodium (Na+), potassium (K+) and calcium (Ca+2).

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

Postsynaptic kainate receptors are involved in excitatory neurotransmission, while presinatics are involved in the inhibitory, modulating the release of GABA through a mechanism presynaptic.

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 AMPA and NMDA receptor subunits.

GluR subunits 5 through 7 can form homomeric channels, that is, making the receptor exclusively composed of one type of those subunits; or heteromeric, 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 through 7.

Molecularly speaking, the ionotropic glutamate receptors are integral membrane proteins, made up of four subunits arranged in a tetramer.

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Distribution

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

1. GluR5 subunit

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

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2. GluR6 subunit

GluR6 is found widely in granule cells of the cerebellum, dentate gyrus, and CA3 region of the hippocampus, 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 brain. deep cerebral cortex and striatum, as well as inhibitory neurons in the molecular layer of the cerebellum.

4. KA1 and KA2 subunits

The KA1 subunit is located in the CA3 region of the hippocampus and it 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 that is formed by kainate receptors is permeable to sodium and potassium ions. its conductance is similar to that of AMPA receptor channels, about 20 pS (petasiemens).

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

synaptic function

As we were previously commenting, kainate receptors are involved in both presynaptic and postsynaptic action. They are found in smaller amounts in the brain than AMPA and NMDA receptors.

The most recent research has discovered that these types of receptors not only have a ionotropic function, directly changing the conductivity of the neuronal membrane, but rather, besides, may involve changes at the metabotropic level, affecting protein production.

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, the research problems in kainate receptors have been linked to various psychological disorders, medical problems and diseases neurodegenerative.

To date, problems in the synaptic function of kainate receptors have been related to ischemia, hypoglycemia, epilepsy, Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, autism spectrum disorders, Huntington's chorea, and amyotrophic lateral sclerosis (ELA.) Most studies have found these relationships with mutations in GluK subunits 1 through 5.

Neuronal plasticity

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 on the presynaptic cell may affect the amount of neurotransmitters to be released into the synaptic gap. This effect can occur quickly and last 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 receivers 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 receivers. Their function in the regulation of GABAergic synaptic transmission in the hippocampus. Neurology magazine. 36. 852-9.