Abstract
A number of kainate receptor antagonists have shown selectivity for receptors containing the GluK1 subunit. Here, we analyze the effects of these GluK1 antagonists on currents mediated by recombinant homomeric GluK3 and heteromeric GluK2/3 receptors expressed in HEK 293 cells and activated by fast application of glutamate. We show that, amongst these compounds, UBP302, UBP310 and UBP316 effectively block recombinant homomeric GluK3 receptors. However, these antagonists are ineffective in blocking homomeric GluK2 or heteromeric GluK2/3 receptors. In addition, these antagonists do not affect presynaptic kainate receptors at mouse hippocampal mossy fibre synapses, which are thought to be composed of GluK2 and GluK3 subunits. Moreover, the AMPA receptor-selective non-competitive antagonist GYKI 53655 blocks, at high concentrations, GluK3-containing receptors and decreases short-term plasticity at mossy fibre synapses. These results expand the range of targets of kainate receptor antagonists and provide pharmacological tools to study the elusive mechanisms of neurotransmitter control by presynaptic kainate receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine / analogs & derivatives
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Alanine / pharmacology
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Animals
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Animals, Newborn
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Benzodiazepines / pharmacology
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Biophysics
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Cell Line, Transformed
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Dose-Response Relationship, Drug
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Excitatory Amino Acid Antagonists / pharmacology*
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Hippocampus / cytology
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Humans
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In Vitro Techniques
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Kainic Acid / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mice
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Mice, Knockout
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Mossy Fibers, Hippocampal / drug effects
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Mossy Fibers, Hippocampal / physiology
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Neuronal Plasticity
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Patch-Clamp Techniques / methods
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Protein Subunits
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Pyramidal Cells / drug effects
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Pyramidal Cells / physiology
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Receptors, Kainic Acid / antagonists & inhibitors*
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Receptors, Kainic Acid / classification
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Receptors, Kainic Acid / genetics
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Receptors, Kainic Acid / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / genetics
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Thymine / analogs & derivatives
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Thymine / pharmacology
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Transfection
Substances
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Excitatory Amino Acid Antagonists
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Protein Subunits
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Receptors, Kainic Acid
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Recombinant Proteins
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UBP 310
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Benzodiazepines
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GYKI 53655
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Alanine
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Thymine
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Kainic Acid