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  • 1
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    Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-09-06
    Description: In the mammalian central nervous system, receptors for excitatory amino acid neurotransmitters such as the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA)-kainate receptor mediate a large fraction of excitatory transmission. Currents induced by activation of the AMPA-kainate receptor were potentiated by agents that specifically stimulate adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase A (PKA) activity or were supported by intracellular application of the catalytic subunit of PKA by itself or in combination with cAMP. Furthermore, depression of these currents by a competitive inhibitor of PKA indicates that AMPA-kainate receptors are regulated by endogenous PKA. Endogenous protein phosphatases also regulate these receptors because an inhibitor of cellular phosphates enhanced kainate currents. Modulation of PKA and phosphatases may regulate the function of these receptors and thus contribute to synaptic plasticity in hippocampal neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, L Y -- Salter, M W -- MacDonald, J F -- New York, N.Y. -- Science. 1991 Sep 6;253(5024):1132-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1653455" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cyclic AMP/pharmacology/physiology ; Ethers, Cyclic/*pharmacology ; Fetus ; Hippocampus/*physiology ; Homeostasis ; Kainic Acid/*metabolism ; Kinetics ; Macromolecular Substances ; Membrane Potentials/drug effects ; Mice ; N-Methylaspartate/pharmacology ; Neurons/drug effects/*physiology ; Okadaic Acid ; Phosphoprotein Phosphatases/*metabolism ; Protein Kinase Inhibitors ; Protein Kinases/*metabolism ; Receptors, Kainic Acid ; Receptors, Neurotransmitter/drug effects/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Phosphorylation and modulation of a kainate receptor (GluR6) by cAMP-dependent protein kinase (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-02-19
    Description: Ligand-gated ion channels gated by glutamate constitute the major excitatory neurotransmitter system in the mammalian brain. The functional modulation of GluR6, a kainate-activated glutamate receptor, by adenosine 3',5'-monophosphate-dependent protein kinase A (PKA) was examined with receptors expressed in human embryonic kidney cells. Kainate-evoked currents underwent a rapid desensitization that was blocked by lectins. Kainate currents were potentiated by intracellular perfusion of PKA, and this potentiation was blocked by co-application of an inhibitory peptide. Site-directed mutagenesis was used to identify the site or sites of phosphorylation on GluR6. Although mutagenesis of two serine residues, Ser684 and Ser666, was required for complete abolition of the PKA-induced potentiation, Ser684 may be the preferred site of phosphorylation in native GluR6 receptor complexes. These results indicate that glutamate receptor function can be directly modulated by protein phosphorylation and suggest that a dynamic regulation of excitatory receptors could be associated with some forms of learning and memory in the mammalian brain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, L Y -- Taverna, F A -- Huang, X P -- MacDonald, J F -- Hampson, D R -- New York, N.Y. -- Science. 1993 Feb 19;259(5098):1173-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8382377" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Brain/*physiology ; Cells, Cultured ; Concanavalin A/pharmacology ; Evoked Potentials/drug effects ; Humans ; Kainic Acid/*pharmacology ; Kidney ; Kinetics ; Membrane Potentials/drug effects ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligodeoxyribonucleotides ; Protein Kinases/*metabolism ; Receptors, Glutamate/drug effects/genetics/*physiology ; Receptors, Kainic Acid ; Serine ; Wheat Germ Agglutinins/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Picrotoxin convulsions involve synaptic and nonsynaptic mechanisms on cultured mouse spinal neurons (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-05-30
    Description: The cellular mechanisms underlying picrotoxin-induced convulsive activity were studied by using mouse spinal neurons growing in tissue culture. Picrotoxin-induced convulsive activity in most but not all of the cells studied. The activity could be inverted by polarizing to positive potentials and eliminated either by decreasing the ratio of calcium to magnesium or by applying tetrodotoxin. When applied locally to individual cells, picrotoxin lowered spike threshold and induced spontaneous firing in some but not all cells tested. The results suggest that picrotoxin-induced convulsive activity involves rapidly summating synaptic activity which may be evoked by high-frequency repetitive firing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barker, J L -- MacDonald, J F -- New York, N.Y. -- Science. 1980 May 30;208(4447):1054-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7375918" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects ; Animals ; Calcium/pharmacology ; Cells, Cultured ; Magnesium/pharmacology ; Membrane Potentials/drug effects ; Mice ; Picrotoxin/*pharmacology ; Seizures/*chemically induced ; Spinal Cord/*drug effects/physiology ; Synapses/*drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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