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|glutamate receptor, ionotropic, kainate 1|
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.
There are five types of kainate receptor subunits, GluR5, GluR6, GluR7, KA1 and KA2, which are similar to AMPA and NMDA receptor subunits and can be arranged in different ways to form a tetramer, a four subunit receptor (Dingledine, 1999). GluR5, 6 and 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, 6 or 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.
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 (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 (Huettner, 2003).
Kainate receptors play a role in both pre- and postsynaptic neurons (Huettner, 2003). They have a somewhat more limited distribution in the brain compared to AMPA and NMDA receptors, and their function is not well defined.
Unlike AMPA receptors, kainate receptors play only a minor role in signaling at synapses (Song and Huganir, 2002). 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 (Contractor et al., 2000; Mayer, 2005). Activating kainate receptors in the presynaptic cell can affect the amount of neurotransmitters that are released (Schmitz et al., 2001; Song and Huganir, 2002; Huettner, 2003; Mayer, 2005). This effect may occur quickly and last for a long time (Schmitz et al., 2001), and the effects of repetitive stimulation of KARs can be additive over time (Mayer, 2005).
- NS102 - Selective of Kainate receptor over AMPA receptor
- Kynurenic acid - endogenous ligand
- Contractor A., Swanson G.T., Sailer A., O'Gorman S., and Heinemann S.F. 2000. Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus. The Journal of Neuroscience, 20(22), 8269-8278. Available.
- Dingledine R., Borges K., Bowie D., Traynelis S.F. 1999. The glutamate receptor ion channels. Pharmacological Reviews, 51(1), 7-62. Available.
- Huettner J.E. 2003. Kainate receptors and synaptic transmission. Progress in Neurobiology, 70(5), 387-407.
- Mayer M.L. 2005. Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Neuron, 45(4), 539-552.
- MRC (Medical Research Council). 2003. Glutamate receptors: Structures and functions. University of Brisotol Centre for Synaptic Plasticity. Available.
- Schmitz D., Mellor J., Nicoll R.A. 2001. Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses. Science, 291(5510), 1972-1976.
- Song, I., Huganir R.L. 2002. Regulation of AMPA receptors during synaptic plasticity. Trends in Neurosciences, 25(11), 578-589.
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