Synaptic kainate receptors

Current Opinion in Neurobiology

Volumn 10, Issue 3, 2000, Pages 342-351

  Frerking, Matthew ^a   Nicoll, Roger A ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; AMPA RECEPTOR; GLUTAMIC ACID; IONOTROPIC RECEPTOR; KAINIC ACID RECEPTOR; POSTSYNAPTIC RECEPTOR; PRESYNAPTIC RECEPTOR;

4 AMINOBUTYRIC ACID RELEASE; HUMAN; HUMAN CELL; NERVE CELL PLASTICITY; PRIORITY JOURNAL; PYRAMIDAL NERVE CELL; REVIEW; SYNAPSE; SYNAPTIC TRANSMISSION;

EID: 0034094173     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(00)00094-5     Document Type: Review

References (60)

1. Bettler B., Mulle C. Neurotransmitter receptors II: AMPA and kainate receptors. Neuropharmacol. 34:1995;123-139.
2. Bleakman D., Lodge D. Neuropharmacology of AMPA and kainate receptors. Neuropharmacol. 37:1998;1187-1204.
3. Chittajallu R., Braithwaite S.P., Clarke V.R.J., Henley J.M. Kainate receptors: subunits, synaptic localization and function. Trends Pharmacol Sci. 20:1999;26-35.
4. Agrawal S.G., Evans R.H. The primary afferent depolarizing action of kainate in the rat. Br J Pharmacol. 87:1986;345-355.
5. Bettler B., Boulter J., Hermans-Borgmeyer I., O'Shea-Greenfield A., Deneris E.S., Moll C., Borgmeyer U., Hollmann M., Heinemann S. Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron. 5:1990;583-595.
6. Egebjerg J., Bettler B., Hermans-Borgmeyer I., Heinemann S. Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature. 351:1991;745-748.
7. Schiffer H.H., Swanson G.T., Heinemann S.F. Rat GluR7 and carboxy-terminus splice variant, GluR7b, are functional kainate receptor subunits with a low sensitivity to glutamate. Neuron. 19:1997;1141-1146.
8. Herb A., Burnashev N., Werner P., Sakmann B., Wisden W., Seeburg P.H. The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron. 8:1992;775-785.
9. Partin K.M., Patneau D.K., Winters C.A., Mayer M.L., Buonanno A. Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A. Neuron. 11:1993;1069-1082.
10. Cui C., Mayer M.L. Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7. J Neurosci. 19:1999;8281-8291. One of the first serious attempts to unravel differences in the properties of heteromeric and homomeric kainate receptors. The authors take advantage of the differences in current-voltage relations between edited and unedited forms of GluR5-7, and monitor changes in this parameter when edited GluR6-7 is coexpressed with unedited GluR5 during activation with GluR5 selective agonists (agonists known to be ineffective on homomeric GluR6-7). This clever approach allows the unambiguous demonstration of coassembly of GluR5-7 in heterologous systems, and heteromeric receptors appear to undergo less desensitization and faster recovery from desensitization than homomers.
11. Wisden W., Seeburg P.H. A complex mosaic of high-affinity kainate receptors in rat brain. J Neurosci. 13:1993;291-298.
12. Lerma J., Paternain A.V., Naranjo J.R., Mellström B. Functional kainate-selective glutamate receptors in cultured hippocampal neurons. Proc Natl Acad Sci USA. 90:1993;11 688-11 692.
13. Huettner J.E. Glutamate receptor channels in rat DRG neurons: activation by kainate and quisqualate and blockade of desensitization by Con A. Neuron. 5:1990;255-266.
14. Paternain A.V., Morales M., Lerma J. Selective antagonism of AMPA receptors unmasks kainate receptor-mediated responses in hippocampal neurons. Neuron. 14:1995;185-189.
15. Wilding T.J., Huettner J.E. Differential antagonism of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid-preferring and kainate-preferring receptoRs by 2,3 benzodiazepines. Mol Pharmacol. 47:1995;582-587.
16. Castillo P.E., Malenka R.C., Nicoll R.A. Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons. Nature. 388:1997;182-186.
17. Vignes M., Collingridge G.L. The synaptic activation of kainate receptors. Nature. 388:1997;179-182.
18. Frerking M., Malenka R.C., Nicoll R.A. Synaptic activation of kainite receptors on hippocampal interneurons. Nat Neurosci. 1:1998;479-486. A study examining the roles of presynaptic and postsynaptic kainate receptors on hippocampal interneurons. We find a strong effect of kainate receptor activation on interneuronal excitability, and discover that kainate receptors in these cells can be synaptically activated. Aside from the widely observed differences in kinetics and size between EPSC KA and EPSC AMPA, the two components of the EPSC behave similarly at this synapse. We also provide preliminary evidence suggesting that the depressant action of kainate on stimulus-evoked IPSCs is a consequence of the increase in interneuronal excitability.
19. ••] reaching many of the same conclusions. This study also makes the important contribution that the EPSC KA on these cells, though small, can be large enough to drive interneuronal spiking. The authors also perform reconstructions of the interneurons, and demonstrate that most major anatomical classes of interneurons in the hippocampus have an EPSC KA.
20. DeVries S.H., Schwartz E.A. Kainate receptors mediate synaptic transmission between cones and 'off' bipolar cells in a mammalian retina. Nature. 397:1999;157-160. The first demonstration of synapses with kainate receptors but no AMPA receptors. The kainate receptors reported here have somewhat different properties than those seen in other systems, with rapid and strong desensitization similar to heterologously expressed receptors. The authors show convincingly that this desensitization limits tonic synaptic transmission at this graded synapse and suggest that this limit keeps the cell within its operating range of voltages during sustained glutamate release.
21. Li P., Wilding T.J., Kim S.J., Calejesan A.A., Huettner J.E., Zhuo M. Kainate receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature. 397:1999;161-164. The authors show kainate receptor-mediated synaptic transmission between primary afferents and dorsal horn sensory neurons in the spinal cord through an impressive array of pharmacological tests. The authors also show that intrathecal injection of a kainate receptor selective agonist, which causes substantial desensitization (and therefore may act to block function), has an antinociceptive effect on behavioral responses to nociceptive heat stimuli, while injection of an AMPA receptor selective antagonist has no effect.
22. Li H., Rogawski M.A. GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro. Neuropharmacol. 37:1998;1279-1286.
23. 2+-permeability are unknown.
24. •] of GluR6-deficient mice. The authors convincingly demonstrate the presence of functional kainate receptors on CA1 pyramidal cells in control animals, which are absent in the knock-out animals. Surprisingly, although GluR6 is expressed in CA1 pyramidal cells and generates a current in response to exogenous agonists, there is no resolvable EPSC KA in these cells. The authors also show that interneuronal kainate receptor functions are not apparently affected by removal of GluR6. Finally, the authors show the first clear demonstration of a segregation of expression of GluR5 and GluR6 in the hippocampus.
25. Paternain A.V., Rodríguez-Moreno A., Villarroel A., Lerma J. Activation and desensitization properties of native and recombinant kainate receptors. Neuropharmacol. 37:1998;1249-1259.
26. Swanson G.T., Heinemann S.F. Heterogeneity of homomeric GluR5 kainate receptor desensitization expressed in HEK293 cells. J Physiol. 513:1998;639-646. An interesting paper demonstrating substantial inter-cell variability in desensitization kinetics of heterologously expressed homomeric GluR5 receptors, with responses to kainate showing either a very rapid desensitization, a slow desensitization, or a biphasic combination of the two. The authors suggest that an unidentified intracellular message might determine the kinetic state of the channel, a possibility reinforced by the observation that slowly desensitizing responses sometimes acquire a rapidly desensitizing component after a few minutes of recording.
27. Clements J.D. Transmitter timecourse in the synaptic cleft - its role in central synaptic function. Trends Neurosci. 19:1996;163-171.
28. Garcia E.P., Mehta S., Blair L.A.C., Wells D.G., Shang J., Fukushima T., Fallon J.R., Garner C.C., Marshall J. SAP90 binds and clusters kainate receptors causing incomplete desensitisation. Neuron. 21:1998;727-739. A nice combination of biochemistry and electrophysiology is used to demonstrate association of heterologously expressed kainate receptors with members of the SAP90/PSD-95 family, and the functional consequences of that association. The authors show that SAP90, a protein enriched in the postsynaptic density, binds to both GluR6 and KA2, and coexpression of SAP90 with GluR6-containing kainate receptors in heterologous expression systems leads to a clustering of the receptors and a reduction in steady-state desensitization. Intriguingly, the authors also note coimmunoprecipitation of GluR6 with SAP97, a presynaptic protein.
29. Mulle C., Sailer A., Perez-Otano I., Dickinson-Anson H., Castillo P.E., Bureau I., Maron C., Gage F.H., Mann J.R., Bettler B., Heinemann S.F. Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice. Nature. 392:1998;601-605. The first study in what will surely be a productive line of research: the study of mice lacking individual kainate receptor genes. GluR6-deficient mice lack an EPSC KA at mossy fiber synapses in the hippocampus, and CA3 cells have a reduced sensitivity to the non-NMDA receptor agonist kainate. This study also provides the first clear demonstration that the epileptogenic activity of systemic kainate administration is mediated by kainate receptors, as this activity is abolished in GluR6-deficient mice.
30. Vignes M., Bleakman D., Lodge D., Collingridge G.L. The synaptic activation of the GluR5 subtype of kainate receptor in area CA3 of the rat hippocampus. Neuropharmacol. 36:1997;1477-1481.
31. Bahn S., Volk B., Wisden W. Kainate receptor gene expression in the developing rat brain. J Neurosci. 14:1994;5525-5547.
32. Swanson G.T., Green T., Heinemann S.F. Kainate receptors exhibit differential sensitivities to (S)-5-iodowillardiine. Mol Pharmacol. 53:1998;942-949.
33. Swanson G.T., Feldmeyer D., Kaneda M., Cull-Candy S.G. Effect of RNA editing and subunit coassembly on single-channel properties of recombinant kainate receptors. J Physiol. 492:1996;129-142.
34. Bortolotto Z.A., Clarke V.R.J., Delany C.M., Parry M.C., Smolders I., Vignes M., Ho K.H., Miu P., Brinton B.T., Fantaske R.et al. Kainate receptors are involved in synaptic plasticity. Nature. 402:1999;297-301. A provocative study in which a new kainate receptor specific antagonist, LY382884, is shown to antagonize GluR5-containing kainate receptors without affecting any other homomeric AMPA/kainate receptor channels, or GluR6/KA2 heteromers. LY382884 also blocks the depression of glutamatergic transmission in the hippocampus induced by ATPA [43], a GluR5-selective agonist, and reduces the kainate receptor-mediated component of the mossy fiber EPSC by about 40%. The authors then report that LY382884 blocks the induction of mossy fiber LTP, and two other, more general, non-NMDA receptor antagonists also block mossy fiber LTP, suggesting a role for kainate receptors in the induction of mossy fiber LTP. However, mossy fiber LTP can, at least in some circumstances, be induced even in the presence of non-NMDA receptor antagonists [35-39], so it seems unlikely that kainate receptors are an essential component in the induction of mossy fiber LTP. Further experiments exploring the possible involvement of kainate receptors as metaplastic regulators of mossy fiber LTP will be of interest.
35. Ito I., Sugiyama H. Roles of glutamate receptors in long-term potentiation at hippocampal mossy fiber synapses. NeuroReport. 2:1991;333-336.
36. 2+ channels in hippocampal mossy fiber synaptic transmission and long-term potentiation. Neuron. 12:1994;261-269.
37. Weisskopf M.G., Nicoll R.A. Presynaptic changes during mossy fibre LTP revealed by NMDA receptor-mediated synaptic responses. Nature. 376:1995;256-259.
38. Tong G., Malenka R.C., Nicoll R.A. Long-term potentiation in cultures of single hippocampal granule cells: a presynaptic form of plasticity. Neuron. 16:1996;1147-1157.
39. Yackel M.F., Kapur A., Johnston D. Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism. Nature Neurosci. 2:1999;625-633.
40. Chittajalu R., Vignes M., Dev K.K., Barnes J.M., Collingridge G.L., Henley J.M. Regulation of glutamate release by presynaptic kainate receptors in the hippocampus. Nature. 379:1996;78-81.
41. Clarke V.R.J., Ballyk B.A., Hoo K.H., Mandelzys A., Pellizzari A., Bath C.P., Thomas J., Sharpe E.F., Davies C.H., Ornstein P.L.et al. A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission. Nature. 389:1997;599-603.
42. Rodríguez-Moreno A., Herreras O., Lerma J. Kainate receptors presynaptically downregulate GABAergic inhibition in the rat hippocampus. Neuron. 19:1997;893-901.
43. Vignes M., Clarke V.R.J., Parry M.J., Bleakman D., Lodge D., Ornstein P.L., Collingridge G.L. The GluR5 subtype of kainate receptor regulates excitatory synaptic transmission in areas CA1 and CA3 of the rat hippocampus. Neuropharmacol. 37:1998;1269-1277.
44. Liu Q-S., Patrylo P.R., Gao X-B., Van Den Pol A.N. Kainate acts at presynaptic receptors to increase GABA release from hypothalamic neurons. J Neurophysiol. 82:1999;1059-1062.
45. Perkinton M.S., Sihra T.S. A high-affinity presynaptic kainate-type glutamate receptor facilitates glutamate exocytosis from cerebral cortex nerve terminals (synaptosomes). Neuroscience. 90:1999;1281-1292.
46. Fisher R.S., Alger B.E. Electrophysiological mechanisms of kainic acid-induced epileptoform activity in the rat hippocampal slice. J Neurosci. 4:1984;1312-1323.
47. Rodríguez-Moreno A., Lerma J. Kainate receptor modulation of GABA release involves a metabotropic function. Neuron. 20:1998;1211-1218. A provocative study suggesting a metabotropic link between presynaptic kainate receptors and the release machinery. The authors show that the kainate receptor-mediated depression of the evoked IPSC is blocked by a number of agents affecting the phospholipase C signaling pathway - including inhibition of protein kinase C (PKC) and blockade of certain G proteins with pertussis toxin - and argue that the ionotropic action of kainate receptors is not required to achieve the depressant action on the IPSC. One surprising corollary of these results is that PKC activation may lead to a depression of the IPSC, which is unexpected because activation of PKC with phorbol esters is widely observed to potentiate synaptic release.
48. ••].
49. Min M-Y., Melyan Z., Kullmann D.M. Synaptically released glutamate reduces γ-aminobutyric acid (GABA)ergic inhibition in the hippocampus via kainate receptors. Proc Natl Acad Sci USA. 96:1999;9932-9937. The authors provide a much-needed physiological relevance to the depressant action of exogenous kainate on stimulus-evoked IPSCs in the hippocampus, by showing that this effect can be stimulated by endogenous synaptically-released glutamate. Tetanic stimulation of glutamatergic afferents causes a small depression of the the evoked IPSC that has the pharmacological profile of a kainate receptor-mediated effect. This result suggests that kainate receptors can lead to a phasic disinhibiton, although it is unclear from these results whether this effect is due to presynaptic kainate receptors detecting glutamate 'spill-over' or somatic kainate receptors which lead to interneuronal spiking during the tetanus.
50. 3H]γ-aminobutyric acid release by kainate receptor activation in rat hippocampal synaptosomes. Eur J Pharmacol. 323:1997;167-172.
51. Schoepp D.D., Jane D.E., Monn J.A. Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacol. 38:1999;1431-1476.
52. o proteins in the rat hippocampus. Mol Pharmacol. 56:1999;429-433. An intriguing report, showing that pharmacological manipulations that uncouple G proteins from their receptors reduce the binding of kainate receptor-selective agonists to hippocampal membranes, analogous to the effects of these manipulations on the affinity of classic metabotropic G-protein-coupled receptors, implying a similar functional role for kainate receptors and metabotropic receptors. The lack of structural similarity between kainate receptors and metabotropic receptors introduces some uncertainty about whether the analogy is strictly valid but, in any case, these results indicate some form of interaction between kainate receptors and G proteins.
53. 2+ influx that coincides with the depression of extracellularly recorded field EPSPs. The authors also show an enhancement of paired-pulse facilitation of the EPSP in response to kainate, reinforcing the conclusion that the depression induced by kainate is, at least in part, presynaptic.
54. MacDermott A.B., Role L.W., Siegelbaum S.A. Presynaptic ionotropic receptors and control of transmitter release. Annu Rev Neurosci. 22:1999;443-485.
55. Charara A., Blankstein E., Smith Y. Presynaptic kainate receptors in the monkey striatum. Neuroscience. 91:1999;1195-1200.
56. König P., Engel A.K., Singer W. Integrator or coincidence detector? The role of the cortical neuron revisited. Trends Neurosci. 19:1996;130-137.
57. Ben-Ari Y. Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience. 14:1985;375-403.
58. Rodríguez-Moreno A., López-Garcia J.C., Lerma J. Two populations of kainate receptors with separate signaling mechanisms in hippocampal interneurons. Proc Natl Acad Sci USA. 97:2000;1293-1298. The authors report that different kainate receptor agonists can cause either an increase in interneuronal spiking, a decrease in evoked IPSC amplitude, or both, depending on the agonist used and the concentration applied. The observation that exogenously applied glutamate causes a decrease in evoked IPSC amplitude in the absence of interneuronal spiking is strong evidence that kainate receptors can affect the evoked IPSC through mechanisms independent of the increase in interneuronal spiking, although it remains unclear how much of the more-widely studied depressant action of kainate can be explained by this spike-independent action. The authors also report that agents affecting metabotropic pathways, including pertussis toxin and inhibitors of protein kinase C, reduce the depressant action of kainate on the evoked IPSC without reducing the kainate-induced increase in spiking. This result is consistent with both proposed models for the presynaptic activity of kainate outlined in Figure 2 of this review.
59. Kamiya H., Ozawa S. Kainate receptor-mediated presynaptic inhibition at the mouse hippocampal mossy fibre synapse. J Physiol. 523:2000;653-665. The authors report that application of low doses of kainate enhance presynaptic excitability, assessed both by measurement of the extracellular fiber volley and by increases in the probability of antidromic firing, and simultaneously decrease both presynaptic calcium influx and transmitter release from the mossy fibre synapse. The enhancement of the fiber volley can be elicited even in the absence of extracellular calcium, ruling out the possibility of an indirect, kainate-induced release of a neuromodulator as the mechanism for this effect and providing strong evidence for a direct presynaptic action of kainate receptors. Higher doses of kainate cause a reduction in excitability, and the authors note that a kainate-induced depolarization of the axon could explain the biphasic effect on excitability - the enhancement by recruitment of subthreshold fibers, and the later depression by voltage-dependent sodium channel inactivation. One unaddressed issue which will be of interest in the future is whether the same action of kainate is responsible for both the increase in excitability and the decrease in synaptic release.
60. Chergui K., Bouron A., Normand E., Mulle C. Functional GluR6 kainate receptors in the striatum: indirect dowregulation of synaptic transmission. J Neurosci. 20:2000;2175-2182. The authors explore the role of GluR6 in the striatum using GluR6 knockout mice. The AMPA/kainate receptor agonist domoate depolarizes striatal neurons and leads to spiking in control but not GluR6 knockout mice, although curiously these receptors do not apparently contribute to the EPSC on these cells. Domoate application also leads to a depression of stimulus-evoked IPSCs onto these cells, which again is absent in GluR6 knockout mice, and this depressant action, but not the domoate-induced depolarization, is blocked by adenosine A2A receptor antagonists. The authors suggest that a domoate-induced excitation leads to adenosine release, which then causes the synaptic inhibition.