title: AMPA receptor activation induces association of G-beta protein with the alpha subunit of the sodium channel in neurons.
abstract: Glutamatergic transmission is mediated by ionotropic receptors that directly gate cationic channels and metabotropic receptors that are coupled to second messenger generating systems and to ionic channels via heterotrimeric guanine-nucleotide binding- (G) proteins. This distinction cannot be made for the ionotropic receptor subclass activated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), which has been shown to be physically associated with the alpha-subunit of Gi1 protein and activates this G-protein. Here, we report that, in addition to a Ca2+ influx, AMPA induces the mobilization of Ca2+ from the mitochondrial pool by reversing the mitochondrial Na+/Ca2+ exchanger in mouse neurons in primary culture. Both processes required the activation of tetrodotoxin-sensitive Na+ channels. AMPA receptor activation modified the gating properties of the Na+ channel, independently of the AMPA current, suggesting a G-protein-mediated process. Indeed, co-immunoprecipitation experiments indicated that AMPA receptor activation induced the association of Gbeta with the alpha-subunit of the Na+ channel. These results suggest that, in addition to its ionic channel function, the AMPA receptor is coupled to Na+ channels through G-proteins and that this novel metabotropic function is involved in the control of neuronal excitability.
authors.affiliation: INSERM U114, Collège de France, 11, Place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: P
authors.initials: P
authors.lastname: Marin
authors.forename: L
authors.initials: L
authors.lastname: Fagni
authors.forename: Y
authors.initials: Y
authors.lastname: Torrens
authors.forename: G
authors.initials: G
authors.lastname: Alcaraz
authors.forename: F
authors.initials: F
authors.lastname: Couraud
authors.forename: J
authors.initials: J
authors.lastname: Bockaert
authors.forename: J
authors.initials: J
authors.lastname: Glowinski
authors.forename: J
authors.initials: J
authors.lastname: Prémont
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005333:Fetus; D020962:Heterotrimeric GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C568249:Scn1a protein, mouse; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin; D020962:Heterotrimeric GTP-Binding Proteins; D002118:Calcium