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Open Access 01-12-2015 | Research

Tumor necrosis factor-α enhances voltage-gated Na⁺ currents in primary culture of mouse cortical neurons

Authors: Weiqiang Chen, Jiangtao Sheng, Jingfang Guo, Fenfei Gao, Xiangfeng Zhao, Jianping Dai, Gefei Wang, Kangsheng Li

Published in: Journal of Neuroinflammation | Issue 1/2015

Abstract

Background

Previous studies showed that TNF-α could activate voltage-gated Na⁺ channels (VGSCs) in the peripheral nervous system (PNS). Since TNF-α is implicated in many central nervous system (CNS) diseases, we examined potential effects of TNF-α on VGSCs in the CNS.

Methods

Effects of TNF-α (1–1000 pg/mL, for 4–48 h) on VGSC currents were examined using whole-cell voltage clamp and current clamp techniques in primary culture of mouse cortical neurons. Expression of Nav1.1, Nav1.2, Nav1.3, and Nav1.6 were examined at both the mRNA and protein levels, prior to and after TNF-α exposure.

Results

TNF-α increased Na⁺ currents by accelerating the activation of VGSCs. The threshold for action potential (AP) was decreased and firing rate were increased. VGSCs were up-regulated at both the mRNA and protein levels. The observed effects of TNF-α on Na⁺ currents were inhibited by pre-incubation with the NF-κB inhibitor BAY 11–7082 (1 μM) or the p38 mitogen-activated protein kinases (MAPK) inhibitor SB203580 (1 μM).

Conclusions

TNF-α increases Na⁺ currents by accelerating the channel activation as well as increasing the expression of VGSCs in a mechanism dependent upon NF-κB and p38 MAPK signal pathways in CNS neurons.

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Title: Tumor necrosis factor-α enhances voltage-gated Na+ currents in primary culture of mouse cortical neurons
Authors: Weiqiang Chen
Jiangtao Sheng
Jingfang Guo
Fenfei Gao
Xiangfeng Zhao
Jianping Dai
Gefei Wang
Kangsheng Li
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-015-0349-x

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Tumor necrosis factor-α enhances voltage-gated Na⁺ currents in primary culture of mouse cortical neurons

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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