Tumor necrosis factor alpha increases cytosolic calcium responses to AMPA and KCl in primary cultures of rat hippocampal neurons

Alok De; James M Krueger; Steven M Simasko

doi:10.1016/S0006-8993(03)02997-4

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Tumor necrosis factor alpha increases cytosolic calcium responses to AMPA and KCl in primary cultures of rat hippocampal neurons

Journal article

Peer reviewed

Tumor necrosis factor alpha increases cytosolic calcium responses to AMPA and KCl in primary cultures of rat hippocampal neurons

Alok De, James M Krueger and Steven M Simasko

Brain research, Vol.981(1-2), pp.133-142

08/15/2003

DOI: https://doi.org/10.1016/S0006-8993(03)02997-4

Handle:

https://hdl.handle.net/2376/100935

PMID: 12885434

Abstract

Calcium - metabolism

Spider Venoms - pharmacology

Dose-Response Relationship, Drug

Drug Interactions

omega-Conotoxin GVIA - pharmacology

Potassium Chloride - pharmacology

Excitatory Amino Acid Agents - pharmacology

6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology

Neurons - metabolism

Protein Synthesis Inhibitors - pharmacology

Neurons - drug effects

Animals, Newborn

Receptors, Tumor Necrosis Factor - metabolism

Peptide Fragments - metabolism

Cells, Cultured

Rats

Excitatory Amino Acid Antagonists - pharmacology

Calcium Channel Blockers - pharmacology

Hippocampus - cytology

Fura-2 - metabolism

Cycloheximide - pharmacology

Agatoxins

Tumor Necrosis Factor-alpha - pharmacology

Animals

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology

Mice

Acute behavioral effects of tumor necrosis factor alpha (TNFalpha) have been previously reported, however the cellular basis for these actions are unknown. To address this issue we examined the effects of TNFalpha on AMPA- and depolarization-induced changes in cytosolic Ca(2+) in cultured hippocampal neurons. Single cell Ca(2+) levels were determined with the fluorescent calcium indicator fura-2. TNFalpha caused an up-regulation of AMPA (10 microM)- and depolarization (55 mM KCl)-induced Ca(2+) responses. This effect occurred within a window of concentrations (1 and 10 ng/ml but not 0.1 or 100 ng/ml) and times (3 and 6 h but not 1 and 24 h). The effect was dependent upon protein synthesis (blocked by cycloheximide) and was prevented by the soluble TNF receptor and by a soluble TNF receptor fragment. Treatment with the soluble TNF receptor fragment also caused a decrease in the basal response. The TNFalpha treatment protocols did not appear to produce any toxicity to the neurons. Results are consistent with the hypothesis that TNFalpha regulates proteins known to be involved in neuronal communication (AMPA receptors) and cell regulation (voltage-dependent calcium channels) in a relatively rapid period of time (a few hours). These actions may be related to the behavioral effects produced by TNFalpha that occur within this time frame.

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Title: Tumor necrosis factor alpha increases cytosolic calcium responses to AMPA and KCl in primary cultures of rat hippocampal neurons
Creators: Alok De - Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, College of Veterinary Medicine, Washington State University, 205 Wegner Hall, Pullman, WA 99164-6520, USA
James M Krueger
Steven M Simasko
Publication Details: Brain research, Vol.981(1-2), pp.133-142
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Netherlands
Grant note: NS 31453 / NINDS NIH HHS NS 25378 / NINDS NIH HHS
Identifiers: 99900546521901842
Language: English
Resource Type: Journal article

Tumor necrosis factor alpha increases cytosolic calcium responses to AMPA and KCl in primary cultures of rat hippocampal neurons

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