Ultrastructural localisation and differential agonist‐induced regulation of AMPA and kainate receptors present at the presynaptic active zone and postsynaptic density

• Published in: Journal of neurochemistry Vol. 99; no. 2; pp. 549 - 560
• Main Authors: Feligioni, Marco, Holman, David, Haglerod, Camilla, Davanger, Svend, Henley, Jeremy M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2006; Blackwell
• Subjects: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; AMPA; Animals; Biochemistry; Biological and medical sciences; Brain; Brain - metabolism; Brain - ultrastructure; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Down-Regulation - drug effects; Down-Regulation - physiology; Excitatory Amino Acid Agonists - pharmacology; Fundamental and applied biological sciences. Psychology; Glutamic Acid - metabolism; kainate; Microscopy, Electron, Transmission; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); N-Methylaspartate - pharmacology; Neurosciences; Organ Culture Techniques; post‐synaptic; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Presynaptic Terminals - ultrastructure; pre‐synaptic; Protein Subunits - agonists; Protein Subunits - metabolism; Rats; Rats, Wistar; Receptors, AMPA - agonists; Receptors, AMPA - metabolism; Receptors, Kainic Acid - agonists; Receptors, Kainic Acid - metabolism; regulation; Rodents; Synapses - drug effects; Synapses - metabolism; Synapses - ultrastructure; Synaptic Membranes - drug effects; Synaptic Membranes - metabolism; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; synaptosomes; Synaptosomes - metabolism; Up-Regulation - drug effects; Up-Regulation - physiology; Vertebrates: nervous system and sense organs; Ionotropic receptor; Separation; AMPA; Rat; synaptosomes; Rodentia; Central nervous system; Glutamate receptor; pre-synaptic; kainate; Encephalon; Kainate receptor; Postsynaptic; Vertebrata; AMPA receptor; Membrane receptor; Mammalia; regulation; Modulation; Synaptic plasticity; post-synaptic; Presynaptic; Biological receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04087.x

Activity‐dependent changes in ionotropic glutamate receptors at the postsynaptic membrane are well established and this regulation plays a central role in the expression of synaptic plasticity. However, very little is known about the distributions and regulation of ionotropic receptors at presynaptic sites. To determine if presynaptic receptors are subject to similar regulatory processes we investigated the localisation and modulation of AMPA (GluR1, GluR2, GluR3) and kainate (GluR6/7, KA2) receptor subunits by ultrasynaptic separation and immunoblot analysis of rat brain synaptosomes. All of the subunits were enriched in the postsynaptic fraction but were also present in the presynaptic and non‐synaptic synaptosome fractions. AMPA stimulation resulted in a marked decrease in postsynaptic GluR2 and GluR3 subunits, but an increase in GluR6/7. Conversely, GluR2 and GluR3 increased in the presynaptic fraction whereas GluR6/7 decreased. There were no significant changes in any of the compartments for GluR1. NMDA treatment decreased postsynaptic GluR1, GluR2 and GluR6/7 but increased presynaptic levels of these subunits. NMDA treatment did not evoke changes in GluR3 localisation. Our results demonstrate that presynaptic and postsynaptic subunits are regulated in opposite directions by AMPA and NMDA stimulation.