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

They are not well known and research, to date, continues to try to elucidate what involvement it has in various disorders, especially epilepsy and diseases such as Alzheimer’s and Parkinson’s. Below we will see what is known about these peculiar ionotropic receptors.

What are kainato receptors?

Kainate receptors are found in the neuronal membrane and respond to the presence of glutamate . They were traditionally classified as non-MDA 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 a 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, participates in the processes of neuronal growth and maturation, as well as being involved in the formation and elimination of synapses, and in the processes of learning and memory formation.

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

Metabotropics are coupled to G-proteins and regulate the production of intracellular messengers .

Ionotropics, where kainate receptors are found , form a cationic channel with different selectivity for certain ions , being permeable to several ions: sodium (Na+), potassium (K+) and calcium (Ca+2).

Among the ionotropic receptors of glutamate are, as 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, while presynaptic receptors are involved in inhibitory neurotransmission, modulating the release of GABA through 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 AMPA and NMDA receptor subunits.

The GluR subunits 5 to 7 can form homomeric channels , that is, make the receiver composed exclusively of one type of these subunits; or heteromers, making it possible to have 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, glutamate ionotropic receptors are integral membrane proteins, formed by four subunits organized in a tetramer .

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Distribution

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

1. Sub-unit GluR5

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

2. Sub-unit GluR6

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

3. Sub-unit GluR7

The GluR7 subunit is rarely found 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. Sub-units KA1 and KA2

The subunit KA1 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 the kainate receptors is permeable to sodium and potassium ions. Its conductance is similar to that of the channels of the AMPA receptors, about 20 pS (petasiemens).

However, kainate receptors differ from MPAs in that the post-synaptic potentials generated by kainate receptors are slower than the post-synaptic potentials of MPAs.

Synaptic function

As we have already mentioned, kainato receptors are involved in both presynaptic and post-synaptic action . They are found in smaller quantities in the brain than the 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 also may involve changes at the metabotropic level, affecting the production of proteins .

It can be said that kainate is an excitotoxic substance, causing seizures and neuronal damage, phenomena very similar to those seen in the neurons of people suffering from epilepsy. Therefore, and taking into account that all this is closely related to problems of neurotransmission of glutamate, 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.

Neural plasticity

Kainate receptors take a rather modest role in synapses compared to AMPA receptors. They play a very subtle role in synaptic plasticity, affecting the probability that the post-synaptic cell will send a response to a future stimulus.

The activation of the kainate receptors in the presynaptic cell may affect the amount of neurotransmitters that will be released in the synaptic space. This effect can occur rapidly and have effects over a long period of time, and repeated stimulation of kanate receptors can become addictive over time.

Bibliographic references:

  • Dingledine R, Borges K, Bowie D, Traynelis SF (March 1999). “The glutamate 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 (Abril 2014). “Papel de los receptores de cainato GluK1 en las convulsiones, las descargas epilépticas y la epileptogénesis”. La Revista de Neurociencia. 34 (17): 5765–75.
  • Rodríguez-Moreno, Antonio. (2003). Receptores de kainato. Su función en la regulación de la transmisión sináptica de GABAergic en el hipocampo. Revista de neurología. 36. 852-9.