title: Slow synaptic inhibition mediated by metabotropic glutamate receptor activation of GIRK channels.
abstract: Glutamate is the predominant excitatory neurotransmitter in the vertebrate CNS. Ionotropic glutamate receptors mediate fast excitatory actions whereas metabotropic glutamate receptors (mGluRs) mediate a variety of slower effects. For example, mGluRs can mediate presynaptic inhibition, postsynaptic excitation, or, more rarely, postsynaptic inhibition. We previously described an unusually slow form of postsynaptic inhibition in one class of projection neuron in the song-control nucleus HVc of the songbird forebrain. These neurons, which participate in a circuit that is essential for vocal learning, exhibit an inhibitory postsynaptic potential (IPSP) that lasts several seconds. Only a portion of this slow IPSP is mediated by GABA(B) receptors. Since these cells are strongly hyperpolarized by agonists of mGluRs, we used intracellular recording from brain slices to investigate the mechanism of this hyperpolarization and to determine whether mGluRs contribute to the slow synaptic inhibition. We report that mGluRs hyperpolarize these HVc neurons by activating G protein-coupled, inwardly-rectifying potassium (GIRK) channels. MGluR antagonists blocked this response and the slow synaptic inhibition. Thus, glutamate can combine with GABA to mediate slow synaptic inhibition by activating GIRK channels in the CNS.
authors.affiliation: Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6074, USA.
authors.forename: P
authors.initials: P
authors.lastname: Dutar
authors.forename: J J
authors.initials: JJ
authors.lastname: Petrozzino
authors.forename: H M
authors.initials: HM
authors.lastname: Vu
authors.forename: M F
authors.initials: MF
authors.lastname: Schmidt
authors.forename: D J
authors.initials: DJ
authors.lastname: Perkel
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018755:GABA Agonists / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D020308:Songbirds; D013569:Synapses / Q000737:chemistry / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: C089837:2-methyl-2-(2-carboxycyclopropyl)glycine; D000600:Amino Acids, Dicarboxylic; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018755:GABA Agonists; D018696:Neuroprotective Agents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018094:Receptors, Metabotropic Glutamate; D013873:Thionucleotides; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013779:Tetrodotoxin; D004533:Egtazic Acid; D019789:Tetraethylammonium; C023427:guanosine 5'-O-(2-thiodiphosphate); D001418:Baclofen; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid