Abstract
Kainate receptor activation depresses synaptic release of neurotransmitter at a number of synapses in the CNS. The mechanism underlying this depression is controversial, and both ionotropic and metabotropic mechanisms have been suggested. We report here that the AMPA/kainate receptor agonists domoate (DA) and kainate (KA) cause a presynaptic depression of glutamatergic transmission at CA3-->CA1 synapses in the hippocampus, which is not blocked by the AMPA receptor antagonist GYKI 53655 but is blocked by the AMPA/KA receptor antagonist CNQX. Neither a blockade of interneuronal discharge nor antagonists of several neuromodulators affect the depression, suggesting that it is not the result of indirect excitation and subsequent release of a neuromodulator. Presynaptic depolarization, achieved via increasing extracellular K(+), caused a depression of the presynaptic fiber volley and an increase in the frequency of miniature EPSCs. Neither effect was observed with DA, suggesting that DA does not depress transmission via a presynaptic depolarization. However, the effects of DA were abolished by the G-protein inhibitors N-ethylmaleimide and pertussis toxin. These results suggest that KA receptor activation depresses synaptic transmission at this synapse via a direct, presynaptic, metabotropic action.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Ethylmaleimide / pharmacology
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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GTP-Binding Proteins / antagonists & inhibitors
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GTP-Binding Proteins / metabolism
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / metabolism*
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In Vitro Techniques
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Kainic Acid / analogs & derivatives*
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Kainic Acid / pharmacology
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Patch-Clamp Techniques
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Pertussis Toxin
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Potassium / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / agonists
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / metabolism
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Receptors, Kainic Acid / agonists
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Receptors, Kainic Acid / metabolism*
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Synapses / drug effects
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Synapses / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Virulence Factors, Bordetella / pharmacology
Substances
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Enzyme Inhibitors
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Receptors, AMPA
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Receptors, Kainic Acid
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Virulence Factors, Bordetella
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Pertussis Toxin
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GTP-Binding Proteins
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domoic acid
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Ethylmaleimide
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Potassium
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Kainic Acid