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AMPA receptor activation induces association of G‐beta protein with the alpha subunit of the sodium channel in neurons
Author(s) -
Marin Philippe,
Fagni Laurent,
Torrens Yvette,
Alcaraz Gisèle,
Couraud François,
Bockaert Joël,
Glowinski Jacques,
Prémont Joël
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01827.x
Subject(s) - ampa receptor , ionotropic effect , chemistry , interleukin 5 receptor alpha subunit , g alpha subunit , ionotropic glutamate receptor , microbiology and biotechnology , metabotropic receptor , kainate receptor , g beta gamma complex , g protein , heterotrimeric g protein , biology , receptor , glutamate receptor , biophysics , protein subunit , biochemistry , gene
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 α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA), which has been shown to be physically associated with the α‐subunit of G i1 protein and activates this G‐protein. Here, we report that, in addition to a Ca 2+ influx, AMPA induces the mobilization of Ca 2+ from the mitochondrial pool by reversing the mitochondrial Na + /Ca 2+ 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 Gβ with the α‐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.