title: Tumor necrosis-factor-alpha (TNF-alpha) induces rapid insertion of Ca2+-permeable alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels in a subset of hippocampal pyramidal neurons.
abstract: The presence of cell surface Ca2+ permeable alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels on subsets of central neurons influences both normal physiological function and vulnerability to excitotoxicity. Factors that regulate the formation and membrane insertion of Ca-A/K channels, however, are poorly understood. Recently, the cytokine tumor necrosis factor-alpha (TNF-alpha) was shown to increase the cell surface expression of an AMPA receptor (AMPAR) subunit (GluR1) and to potentiate vulnerability to AMPAR-mediated injury. In this study, we examined the possibility that TNF-alpha might also increase numbers of functional Ca-A/K channels. In acute hippocampal slice preparations, TNF-alpha appeared to increase Ca-A/K channel numbers in pyramidal neurons (HPNs), as assessed using a histochemical stain based on kainate-induced uptake of Co2+ ions (Co2+ labeling). In dissociated hippocampal neuronal cultures, TNF-alpha exposure (6 nM, 15 min) induced a rapid increase in cell surface levels not only of GluR1, but also of the AMPAR subunit GluR2, on most neurons, without evident new protein synthesis. Furthermore, consistent with the slice studies, fluorescence Ca2+ imaging techniques revealed an increase in numbers of Ca-A/K channels on what appeared to be a subset of HPNs. These observations are the first to provide evidence for the rapid upregulation of neuronal Ca-A/K channels in response to a cytokine or any other soluble factor, and provide a novel mechanism through which TNF-alpha may modulate both synaptic function and neuronal vulnerability.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697-4292, USA.
authors.forename: Fumio
authors.initials: F
authors.lastname: Ogoshi
authors.forename: Hong Zhen
authors.initials: HZ
authors.lastname: Yin
authors.forename: Yuvarani
authors.initials: Y
authors.lastname: Kuppumbatti
authors.forename: Bora
authors.initials: B
authors.lastname: Song
authors.forename: Simin
authors.initials: S
authors.lastname: Amindari
authors.forename: John H
authors.initials: JH
authors.lastname: Weiss
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D003035:Cobalt / Q000493:pharmacokinetics; D003952:Diagnostic Imaging / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014966:Xanthenes / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; D018690:Excitatory Amino Acid Agonists; C409648:Fluo 4; D021122:Protein Subunits; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D014409:Tumor Necrosis Factor-alpha; D014966:Xanthenes; D003035:Cobalt; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005968:Glutamate Decarboxylase; D002118:Calcium