- Kainate receptor
Kainate receptors, or KARs, are non-
NMDA ionotropic receptor s which respond to the neurotransmitterglutamate . They were first identified as a distinct receptor type through their selective activation by the agonistkainate , a drug first isolated from "redalga Digenea simplex". KARs are less well understood than AMPA andNMDA receptor s, the otherionotropic glutamate receptor s. Kainate receptors are involved in excitatoryneurotransmission by activating postsynaptic receptors, and in inhibitoryneurotransmission by modulating release of the inhibitory neurotransmitterGABA 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 atetramer , 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 thecytoplasm ic face of the membrane, pushes into thecell 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 tosodium andpotassium 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 neuron s. ] They have a somewhat more limited distribution in thebrain compared to AMPA and NMDA receptors, and their function is not well defined.KARs have been implicated in causing
epilepsy andsensory transduction .Plasticity
Unlike AMPA receptors, kainate receptors play only a minor role in signaling at
synapse s.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 ofneurotransmitter s 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
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CNQX
*DNQX
*NS102 - Selective of Kainate receptor overAMPA receptor
*Kynurenic acid - endogenous ligand
*Tezampanel ee also
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NMDA receptor
*AMPA receptor
*Long term potentiation References
External links
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