title: A kainate receptor increases the efficacy of GABAergic synapses.
abstract: Brain functions are based on the dynamic interaction of excitatory and inhibitory inputs. Spillover of glutamate from excitatory synapses may diffuse to and modulate nearby inhibitory synapses. By recording unitary inhibitory postsynaptic currents (uIPSCs) from cell pairs in CA1 of the hippocampus, we demonstrated that low concentrations of Kainate receptor (KAR) agonists increased the success rate (P(s)) of uIPSCs, whereas high concentrations of KAR agonists depressed GABAergic synapses. Ambient glutamate released by basal activities or stimulation of the stratum radiatum increases the efficacy of GABAergic synapses by activating presynaptic KARs, which facilitate Ca(2+)-dependent GABA release. The results suggest that glutamate released from excitatory synapses may also function as an intermediary between excitatory and inhibitory synapses to protect overexcitation of local circuits.
authors.affiliation: Department of Cell Biology and Anatomy, New York Medical College, Basic Science Building, Room 220, Valhalla, NY 10595, USA.
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Nedergaard
authors.forename: J
authors.initials: J
authors.lastname: Kang
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000819:agonists / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001565:Benzoates; D001569:Benzodiazepines; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D005998:Glycine; D007608:Kainic Acid; D011493:Protein Kinase C; D011810:Quinoxalines; D018092:Kainic Acid Receptors; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C079694:alpha-methyl-4-carboxyphenylglycine; C085266:talampanel