Pharmacological characterization of an unusual mGluR-evoked neuronal hyperpolarization mediated by activation of GIRK channels.
The metabotropic glutamate receptor (mGluR) agonist ACPD exerts an unusual inhibitory effect on a population of neurons of the song-control nucleus HVc of the zebra finch via activation of the GIRK channel. We report in the present study the pharmacology of this response. ACPD directly hyperpolarized the neurons by a mechanism independent of GABA(B) receptors. The group I mGluR agonist DHPG had no effect on membrane properties and the group I mGluR antagonist 4-CPG did not affect the ACPD-induced hyperpolarization. In contrast, the ACPD response was mimicked by the group II mGluR agonist LY314593 and the group II and III agonist L-CCG-I. The group II mGluR antagonist LY307452 fully antagonized the ACPD response and reduced the response induced by L-CCG-I. The group III mGluR agonist L-AP4 induced a small hyperpolarization, which was antagonized by the group III mGluR antagonist MAP-4. These data indicate that group II and group III mGluRs are present and functional in the postsynaptic membrane of these HVc neurons, and mediate the hyperpolarizing action of mGluR agonists. In contrast, group I mGluRs are absent from these neurons, nonfunctional, or coupled to different effector systems that do not influence membrane potential or input resistance.
Dutar
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Department of Neuroscience, University of Pennsylvania, Philadelphia 19104-6074, USA.
Vu
H M
HM
Perkel
D J
DJ
D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000819:agonists*; D024661:Potassium Channels, Inwardly Rectifying; D018080:Receptors, GABA-B / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D020308:Songbirds / Q000502:physiology*; D014828:Vocalization, Animal / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane