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Gene Review

GRIK4  -  glutamate receptor, ionotropic, kainate 4

Homo sapiens

Synonyms: EAA1, Excitatory amino acid receptor 1, GRIK, GluK4, Glutamate receptor KA-1, ...
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Disease relevance of GRIK4

  • When we targeted the N-methyl-D-aspartic acid (NMDA) excitatory amino acid receptor with an AAV-delivered antisense oligonucleotide, however, the promoter determined whether focal seizure sensitivity was significantly attenuated or facilitated [1].
  • These observations suggest that hyperalgesia and morphine tolerance may be interrelated at the level of the superficial laminae of the dorsal horn by common neural substrates that interact at the level of excitatory amino acid receptor activation and subsequent intracellular events [2].
  • The immunohistochemical study with KA1 revealed that the surviving myocytes included in the infarcted region, especially in the ventricular aneurysm, expressed ir-ALC1 strongly in comparison with those in the noninfarcted or the control ventricles [3].
  • Whole-cell recordings of amacrine and ganglion cells in the superfused retina-eyecup preparation of the mudpuppy were obtained in order to determine which excitatory amino acid receptor (EAAR) subtype mediates the synaptic responses of these neurons [4].
  • Monoclonal antibody KA1 stained preferentially the basal-myoepithelial cells of the normal breast and FCD while staining tumor cell subpopulations in 4 of 31 carcinomas [5].

Psychiatry related information on GRIK4


High impact information on GRIK4


Chemical compound and disease context of GRIK4


Biological context of GRIK4


Anatomical context of GRIK4

  • A neuron's combination of excitatory amino acid receptor subunits may regulate its response to excitatory inputs and further defines the role of identified subclasses of neurons in the complex circuitry of the cerebral cortex and may also indicate the basis for the apparent cellular selectivity of excitotoxic degenerative processes [21].
  • The data indicate that the regional and cellular distribution of KA receptor subunit mRNAs in human hippocampus, neocortex and cerebellum largely parallels that in the corresponding areas of rat brain, albeit at lower levels, especially with regard to GluR5 and KA1 transcripts [22].
  • KA1 mRNA was detected in the dentate gyrus but not reliably elsewhere [22].
  • In the cerebral cortex, KA1-like immunostaining was observed in many pyramidal neuron somata, mainly in layer V, and along their apical dendrites [23].
  • Here, we describe the presence of KA1-like immunoreactivity in both neurons and glial cells of the CNS, using a newly developed antiserum to a specific carboxy terminus epitope of the KA1 subunit [23].

Associations of GRIK4 with chemical compounds

  • Here we report association studies of schizophrenia with polymorphisms in three kainate receptor genes: GRIK3, GRIK4 and GRIK5 [18].
  • Ethanol inhibited to a similar extent KA-gated currents mediated by receptors composed of either GluR6 or GluR6 + KA1 subunits, and to a slightly lesser extent receptors composed of GluR6 + KA2 subunits [24].
  • The mRNAs encoding kainic acid (KA) preferring glutamate receptor subunits (GluR5-7, KA1 and KA2) are differentially expressed in rat brain [22].
  • In man propiverine is bound to serum albumin at a single site with high affinity (KA1 = 1.45 x 10(4) L mol-1) and at least two sites with low affinity (KA2 = 2.5 x 10(2) L mol-1) [25].
  • Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63% [26].

Physical interactions of GRIK4


Regulatory relationships of GRIK4


Other interactions of GRIK4


Analytical, diagnostic and therapeutic context of GRIK4


  1. Attenuation of seizures and neuronal death by adeno-associated virus vector galanin expression and secretion. Haberman, R.P., Samulski, R.J., McCown, T.J. Nat. Med. (2003) [Pubmed]
  2. Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions. Mayer, D.J., Mao, J., Holt, J., Price, D.D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. Increased expression and regional differences of atrial myosin light chain 1 in human ventricles with old myocardial infarction. Analyses using two monoclonal antibodies. Nakao, K., Yasue, H., Fujimoto, K., Jougasaki, M., Yamamoto, H., Hitoshi, Y., Takatsu, K., Miyamoto, E. Circulation (1992) [Pubmed]
  4. Do N-methyl-D-aspartate receptors mediate synaptic responses in the mudpuppy retina? Coleman, P.A., Miller, R.F. J. Neurosci. (1988) [Pubmed]
  5. Coexpression patterns of vimentin and glial filament protein with cytokeratins in the normal, hyperplastic, and neoplastic breast. Gould, V.E., Koukoulis, G.K., Jansson, D.S., Nagle, R.B., Franke, W.W., Moll, R. Am. J. Pathol. (1990) [Pubmed]
  6. Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder. Pickard, B.S., Malloy, M.P., Christoforou, A., Thomson, P.A., Evans, K.L., Morris, S.W., Hampson, M., Porteous, D.J., Blackwood, D.H., Muir, W.J. Mol. Psychiatry (2006) [Pubmed]
  7. Excitatory amino acid binding sites in the caudate nucleus and frontal cortex of Huntington's disease. Dure, L.S., Young, A.B., Penney, J.B. Ann. Neurol. (1991) [Pubmed]
  8. Non-plaque dystrophic dendrites in Alzheimer hippocampus: a new pathological structure revealed by glutamate receptor immunocytochemistry. Aronica, E., Dickson, D.W., Kress, Y., Morrison, J.H., Zukin, R.S. Neuroscience (1998) [Pubmed]
  9. Anthropometric indices and life style practices of the indigenous Orang Asli adults in Lembah Belum, Grik of Peninsular Malaysia. Yusof, H.M., Ching, T.S., Ibrahim, R., Lola, S. Asia Pacific journal of clinical nutrition (2007) [Pubmed]
  10. Regulation of NMDA receptors by tyrosine kinases and phosphatases. Wang, Y.T., Salter, M.W. Nature (1994) [Pubmed]
  11. Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Werner, P., Voigt, M., Keinänen, K., Wisden, W., Seeburg, P.H. Nature (1991) [Pubmed]
  12. Recent advances in the pharmacology of the vestibulo-ocular reflex system. Smith, P.F., Darlington, C.L. Trends Pharmacol. Sci. (1996) [Pubmed]
  13. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Krystal, J.H., Karper, L.P., Seibyl, J.P., Freeman, G.K., Delaney, R., Bremner, J.D., Heninger, G.R., Bowers, M.B., Charney, D.S. Arch. Gen. Psychiatry (1994) [Pubmed]
  14. Pharmacological and functional characteristics of metabotropic excitatory amino acid receptors. Schoepp, D., Bockaert, J., Sladeczek, F. Trends Pharmacol. Sci. (1990) [Pubmed]
  15. Plasmid pCAR3 Contains Multiple Gene Sets Involved in the Conversion of Carbazole to Anthranilate. Urata, M., Uchimura, H., Noguchi, H., Sakaguchi, T., Takemura, T., Eto, K., Habe, H., Omori, T., Yamane, H., Nojiri, H. Appl. Environ. Microbiol. (2006) [Pubmed]
  16. Dysfunction of brain kynurenic acid metabolism in Huntington's disease: focus on kynurenine aminotransferases. Jauch, D., Urbańska, E.M., Guidetti, P., Bird, E.D., Vonsattel, J.P., Whetsell, W.O., Schwarcz, R. J. Neurol. Sci. (1995) [Pubmed]
  17. The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat. Szpirer, C., Molné, M., Antonacci, R., Jenkins, N.A., Finelli, P., Szpirer, J., Riviere, M., Rocchi, M., Gilbert, D.J., Copeland, N.G. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  18. Association study of polymorphisms in the GluR7, KA1 and KA2 kainate receptor genes (GRIK3, GRIK4, GRIK5) with schizophrenia. Shibata, H., Aramaki, T., Sakai, M., Ninomiya, H., Tashiro, N., Iwata, N., Ozaki, N., Fukumaki, Y. Psychiatry research. (2006) [Pubmed]
  19. Significant linkage to migraine with aura on chromosome 11q24. Cader, Z.M., Noble-Topham, S., Dyment, D.A., Cherny, S.S., Brown, J.D., Rice, G.P., Ebers, G.C. Hum. Mol. Genet. (2003) [Pubmed]
  20. Properties of immunoglobulin G-Fc receptors from neonatal rat intestinal brush borders. Simister, N., Rees, A.R. Ciba Found. Symp. (1983) [Pubmed]
  21. Quantitative localization of AMPA/kainate and kainate glutamate receptor subunit immunoreactivity in neurochemically identified subpopulations of neurons in the prefrontal cortex of the macaque monkey. Vickers, J.C., Huntley, G.W., Edwards, A.M., Moran, T., Rogers, S.W., Heinemann, S.F., Morrison, J.H. J. Neurosci. (1993) [Pubmed]
  22. Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Porter, R.H., Eastwood, S.L., Harrison, P.J. Brain Res. (1997) [Pubmed]
  23. KA1-like kainate receptor subunit immunoreactivity in neurons and glia using a novel anti-peptide antibody. Fogarty, D.J., Pérez-Cerdá, F., Matute, C. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  24. Acute effects of ethanol on kainate receptors with different subunit compositions. Valenzuela, C.F., Cardoso, R.A. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  25. In-vitro binding of propiverine hydrochloride and some of its metabolites to serum albumin in man. Meisel, P., Langner, S., Siegmund, W. J. Pharm. Pharmacol. (1997) [Pubmed]
  26. Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy. McDonald, J.W., Garofalo, E.A., Hood, T., Sackellares, J.C., Gilman, S., McKeever, P.E., Troncoso, J.C., Johnston, M.V. Ann. Neurol. (1991) [Pubmed]
  27. Novel functions for subtypes of metabotropic glutamate receptors. Schoepp, D.D. Neurochem. Int. (1994) [Pubmed]
  28. Metabotropic excitatory amino acid receptor activation stimulates phospholipase D in hippocampal slices. Boss, V., Conn, P.J. J. Neurochem. (1992) [Pubmed]
  29. Kainate/AMPA receptors expressed on human fetal astrocytes in long-term culture. Cauley, K., Kukekov, V., Young, D. J. Neurosci. Res. (1997) [Pubmed]
  30. Ethanol-induced inhibition of NMDA receptor channels. Wirkner, K., Poelchen, W., Köles, L., Mühlberg, K., Scheibler, P., Allgaier, C., Illes, P. Neurochem. Int. (1999) [Pubmed]
  31. Microzonal decreases in the immunostaining for non-NMDA ionotropic excitatory amino acid receptor subunits GluR 2/3 and GluR 5/6/7 in the human epileptogenic neocortex. DeFelipe, J., Huntley, G.W., del Río, M.R., Sola, R.G., Morrison, J.H. Brain Res. (1994) [Pubmed]
  32. Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia. Von Bergen, N.H., Subieta, A., Brennan, T.J. Anesthesiology (2002) [Pubmed]
  33. Distinct laminar differences in the distribution of excitatory amino acid receptors in adult ferret primary visual cortex. Smith, A.L., Thompson, I.D. Neuroscience (1994) [Pubmed]
  34. NR2B selective NMDA receptor antagonists. Nikam, S.S., Meltzer, L.T. Curr. Pharm. Des. (2002) [Pubmed]
  35. Molecular analysis of excitatory amino acid receptor expression in the cochlea. Niedzielski, A.S., Safieddine, S., Wenthold, R.J. Audiol. Neurootol. (1997) [Pubmed]
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