title: Superactivation of AMPA receptors by auxiliary proteins.
abstract: Glutamate receptors form complexes in the brain with auxiliary proteins, which control their activity during fast synaptic transmission through a seemingly bewildering array of effects. Here we devise a way to isolate the activation of complexes using polyamines, which enables us to show that transmembrane AMPA receptor regulatory proteins (TARPs) exert their effects principally on the channel opening reaction. A thermodynamic argument suggests that because TARPs promote channel opening, receptor activation promotes AMPAR-TARP complexes into a superactive state with high open probability. A simple model based on this idea predicts all known effects of TARPs on AMPA receptor function. This model also predicts unexpected phenomena including massive potentiation in the absence of desensitization and supramaximal recovery that we subsequently detected in electrophysiological recordings. This transient positive feedback mechanism has implications for information processing in the brain, because it should allow activity-dependent facilitation of excitatory synaptic transmission through a postsynaptic mechanism.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Straβe 10, 13125 Berlin, Germany.|NeuroCure, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Carbone
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Straβe 10, 13125 Berlin, Germany.|NeuroCure, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Andrew J R
authors.initials: AJ
authors.lastname: Plested
mesh_terms: D015220:Calcium Channels / Q000378:metabolism*; D025461:Feedback, Physiological; D018698:Glutamic Acid; D057809:HEK293 Cells; D006801:Humans; D017774:Long-Term Potentiation; D008958:Models, Molecular; D018408:Patch-Clamp Techniques; D011073:Polyamines; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: C491912:CACNG2 protein, human; D015220:Calcium Channels; D011073:Polyamines; D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2