title: Kainate receptors depress excitatory synaptic transmission at CA3-->CA1 synapses in the hippocampus via a direct presynaptic action.
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.
authors: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143-0450, USA.
authors: M
authors: M
authors: Frerking
authors: D
authors: D
authors: Schmitz
authors: Q
authors: Q
authors: Zhou
authors: J
authors: J
authors: Johansen
authors: R A
authors: RA
authors: Nicoll
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000819:agonists / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005033:Ethylmaleimide; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D019204:GTP-Binding Proteins; D007608:Kainic Acid; D037342:Pertussis Toxin; D011188:Potassium; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D010566:Virulence Factors, Bordetella; C012301:domoic acid