title: Inflammation alters trafficking of extrasynaptic AMPA receptors in tonically firing lamina II neurons of the rat spinal dorsal horn.
abstract: Peripheral inflammation alters AMPA receptor (AMPAR) subunit trafficking and increases AMPAR Ca(2+) permeability at synapses of spinal dorsal horn neurons. However, it is unclear whether AMPAR trafficking at extrasynaptic sites of these neurons also changes under persistent inflammatory pain conditions. Using patch-clamp recording combined with Ca(2+) imaging and cobalt staining, we found that, under normal conditions, an extrasynaptic pool of AMPARs in rat substantia gelatinosa (SG) neurons of spinal dorsal horn predominantly consists of GluR2-containing Ca(2+)-impermeable receptors. Maintenance of complete Freund's adjuvant (CFA)-induced inflammation was associated with a marked enhancement of AMPA-induced currents and [Ca(2+)](i) transients in SG neurons, while, as we previously showed, the amplitude of synaptically evoked AMPAR-mediated currents was not changed 24 h after CFA. These findings indicate that extrasynaptic AMPARs are upregulated and their Ca(2+) permeability increases dramatically. This increase occurred in SG neurons characterized by intrinsic tonic firing properties, but not in those exhibited strong adaptation. This increase was also accompanied by an inward rectification of AMPA-induced currents and enhancement of sensitivity to a highly selective Ca(2+)-permeable AMPAR blocker, IEM-1460. Electron microcopy and biochemical assays additionally showed an increase in the amount of GluR1 at extrasynaptic membranes in dorsal horn neurons 24h post-CFA. Taken together, our findings indicate that CFA-induced inflammation increases functional expression and proportion of extrasynaptic GluR1-containing Ca(2+)-permeable AMPARs in tonically firing excitatory dorsal horn neurons, suggesting that the altered extrasynaptic AMPAR trafficking might participate in the maintenance of persistent inflammatory pain.
authors.affiliation: Department of General Physiology of Nervous System, Bogomoletz Institute of Physiology, Kiev 01024, Ukraine Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Anesthesiology, Lin-Kou Medical Center, Chung Gung Memorial Hospital, Taoyaun County, Taiwan 333, ROC Laboratory of Neurochemistry, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Kopach
authors.forename: Sheng-Chin
authors.initials: SC
authors.lastname: Kao
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.forename: Pavel
authors.initials: P
authors.lastname: Belan
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Tao
authors.forename: Nana
authors.initials: N
authors.lastname: Voitenko
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D019921:Biotinylation / Q000379:methods; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000009:adverse effects; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D007608:Kainic Acid / Q000009:adverse effects; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D018408:Patch-Clamp Techniques / Q000379:methods; D020671:Posterior Horn Cells / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013116:Spinal Cord / Q000473:pathology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D002118:Calcium; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005620:Freund's Adjuvant; D007608:Kainic Acid; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C104722:glutamate receptor ionotropic, AMPA 2