Kainate receptor

Kainate receptor

Kainate receptors, or KARs, are non-NMDA 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 alga Digenea simplex". KARs are less well understood than AMPA and NMDA receptors, the other ionotropic glutamate receptors. Kainate receptors are involved in excitatory neurotransmission by activating postsynaptic receptors, and in inhibitory neurotransmission by modulating release of the inhibitory neurotransmitter GABA through a presynaptic mechanism.

tructure

There are five types of kainate receptor subunits, GluR5 (Gene|GRIK1), GluR6 (Gene|GRIK2), GluR7 (Gene|GRIK3), KA1 (GRIK4) and KA2 (Gene|GRIK5), which are similar to AMPA and NMDA receptor subunits and can be arranged in different ways to form a tetramer, a four subunit receptor.cite journal | author = Dingledine R, Borges K, Bowie D, Traynelis SF | title = The glutamate receptor ion channels | journal = Pharmacol. Rev. | volume = 51 | issue = 1 | pages = 7–61 | year = 1999 | pmid = 10049997 | doi = | issn = | url = http://pharmrev.aspetjournals.org/cgi/content/abstract/51/1/7 | format = abstract ] 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 an extracellular N-terminal segment, which forms part of the neurotransmitter binding cleft called S1. This segment then passes through the cell membrane, forming the first of three membrane spanning regions called M1. The M2 segment then begins on the cytoplasmic face of the membrane, pushes into the cell membrane 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 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 channel formed by kainate receptors is permeable to sodium and potassium 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. 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.cite journal |author=Huettner JE |title=Kainate receptors and synaptic transmission |journal=Prog. Neurobiol. |volume=70 |issue=5 |pages=387–407 |year=2003 |pmid=14511698 |doi=10.1016/S0301-0082(03)00122-9 ]

Roles

Kainate receptors play a role in both pre- and postsynaptic neurons. ] They have a somewhat more limited distribution in the brain compared to AMPA and NMDA receptors, and their function is not well defined.

KARs have been implicated in causing epilepsy and sensory transduction.

Plasticity

Unlike AMPA receptors, kainate receptors play only a minor role in signaling at synapses.Song, I., Huganir R.L. 2002. [http://www.ingentaconnect.com/content/els/01662236/2002/00000025/00000011/art02270 Regulation of AMPA receptors during synaptic plasticity.] "Trends in Neurosciences," 25(11), 578–589. ]

Rather, kainate receptors may have a more subtle role in synaptic plasticity, affecting the likelihood that the postsynaptic cell will fire in response to future stimulation.cite journal | author = Contractor A, Swanson GT, Sailer A, O'Gorman S, Heinemann SF | title = Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus | journal = J. Neurosci. | volume = 20 | issue = 22 | pages = 8269–78 | year = 2000 | pmid = 11069933 | doi = | issn = | url = http://www.jneurosci.org/cgi/content/abstract/20/22/8269 | format = abstract ] cite journal |author=Mayer ML |title=Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity |journal=Neuron |volume=45 |issue=4 |pages=539–52 |year=2005 |pmid=15721240 |doi=10.1016/j.neuron.2005.01.031] Activating kainate receptors in the presynaptic cell can affect the amount of neurotransmitters that are releasedcite journal |author=Schmitz D, Mellor J, Nicoll RA |title=Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses |journal=Science |volume=291 |issue=5510 |pages=1972–6 |year=2001 |pmid=11239159 |doi=10.1126/science.1057105] ] ] ] 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

* CNQX
* DNQX
* NS102 - Selective of Kainate receptor over AMPA receptor
* Kynurenic acid - endogenous ligand
* Tezampanel

ee also

*NMDA receptor
*AMPA receptor
*Long term potentiation

References

External links

*


Wikimedia Foundation. 2010.

Игры ⚽ Нужно сделать НИР?

Look at other dictionaries:

  • Receptor (biochemistry) — For other uses, see Receptor (disambiguation). In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism. These signals… …   Wikipedia

  • Receptor — In cell biology, a structure on the surface of a cell (or inside a cell) that selectively receives and binds a specific substance. There are hoards of receptors. There are receptors for insulin, receptors for low density lipoproteins (LDL), etc.… …   Medical dictionary

  • kainate — An agonist for the K type excitatory amino acid receptor. It can act as an excitotoxin producing symptoms similar to those of Huntington s chorea, and is also used as an anthelminthic drug. Originally isolated from the alga Digenea simplex. The… …   Dictionary of molecular biology

  • AMPA receptor — The alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is a non NMDA type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the …   Wikipedia

  • Metabotropic receptor — is a subtype of membrane receptors at the surface or in vesicles of eukaryotic cells. In the nervous system, based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories:… …   Wikipedia

  • NMDA receptor — NMDA Glutamic acid …   Wikipedia

  • Cell surface receptor — The seven transmembrane α helix structure of a G protein coupled receptor Cell surface receptors (membrane receptors, transmembrane receptors) are specialized integral membrane proteins that take part in communication between the cell and the… …   Wikipedia

  • NMDA receptor antagonist — Ketamine, one of the most common NMDA receptor antagonists. NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N methyl d aspartate receptor (NMDAR). They are used as anesthesia for animals …   Wikipedia

  • Neurotransmitter receptor — Figure 1. The seven transmembrane α helix structure of a G protein coupled receptor. A Neurotransmitter receptor is a membrane receptor protein[1] that is activated by a Neurotransmitter …   Wikipedia

  • Nicotinic acetylcholine receptor — Acetylcholine Nicotine …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”