title: Pre-synaptic GABA receptors inhibit glutamate release through GIRK channels in rat cerebral cortex.
abstract: Neuronal G protein-gated inwardly rectifying potassium (GIRK) channels mediate the slow inhibitory effects of many neurotransmitters post-synaptically. However, no evidence exists that supports that GIRK channels play any role in the inhibition of glutamate release by GABA(B) receptors. In this study, we show for the first time that GABA(B) receptors operate through two mechanisms in nerve terminals from the cerebral cortex. As shown previously, GABA(B) receptors reduces glutamate release and the Ca(2+) influx mediated by N-type Ca(2+) channels in a mode insensitive to the GIRK channel blocker tertiapin-Q and consistent with direct inhibition of this voltage-gated Ca(2+) channel. However, by means of weak stimulation protocols, we reveal that GABA(B) receptors also reduce glutamate release mediated by P/Q-type Ca(2+) channels, and that these responses are reversed by the GIRK channel blocker tertiapin-Q. Consistent with the functional interaction between GABA(B) receptors and GIRK channels at nerve terminals we demonstrate by immunogold electron immunohistochemistry that pre-synaptic boutons of asymmetric synapses co-express GABA(B) receptors and GIRK channels, thus suggesting that the functional interaction of these two proteins, found at the post-synaptic level, also occurs at glutamatergic nerve terminals.
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ladera
authors.forename: María
authors.initials: M
authors.lastname: del Carmen Godino
authors.forename: María
authors.initials: M
authors.lastname: José Cabañero
authors.forename: Magdalena
authors.initials: M
authors.lastname: Torres
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Rafael
authors.initials: R
authors.lastname: Luján
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Prieto
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology*; D018682:GABA Agents / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D046529:Microscopy, Electron, Transmission / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D018079:Receptors, GABA / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020867:omega-Agatoxin IVA / Q000494:pharmacology
chemical_list: D001514:Bee Venoms; D002121:Calcium Channel Blockers; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018682:GABA Agents; D026902:Potassium Channel Blockers; D018079:Receptors, GABA; D020867:omega-Agatoxin IVA; C029738:tertiapin; D018698:Glutamic Acid; D011189:Potassium Chloride; D002118:Calcium