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肿瘤坏死因子-α增强小鼠皮层神经元原代培养中的电压门控性钠电流。

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

作者信息

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

机构信息

Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, , Guangdong, China.

Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, 515041, , Guangdong, China.

出版信息

J Neuroinflammation. 2015 Jun 26;12:126. doi: 10.1186/s12974-015-0349-x.

DOI:10.1186/s12974-015-0349-x
PMID:26112872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4510892/
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.

摘要

背景

先前的研究表明，肿瘤坏死因子-α（TNF-α）可激活外周神经系统（PNS）中的电压门控钠通道（VGSCs）。由于TNF-α与许多中枢神经系统（CNS）疾病有关，我们研究了TNF-α对CNS中VGSCs的潜在影响。

方法

在小鼠皮质神经元原代培养物中，使用全细胞膜片钳和电流钳技术检测TNF-α（1 - 1000 pg/mL，作用4 - 48小时）对VGSC电流的影响。在TNF-α暴露之前和之后，在mRNA和蛋白质水平检测Nav1.1、Nav1.2、Nav1.3和Nav1.6的表达。

结果

TNF-α通过加速VGSCs的激活增加了钠电流。动作电位（AP）阈值降低，发放率增加。VGSCs在mRNA和蛋白质水平均上调。预先用NF-κB抑制剂BAY 11 - 7082（1 μM）或p38丝裂原活化蛋白激酶（MAPK）抑制剂SB203580（1 μM）孵育可抑制TNF-α对钠电流的观察效应。

结论

在中枢神经系统神经元中，TNF-α通过加速通道激活以及增加VGSCs的表达来增加钠电流，其机制依赖于NF-κB和p38 MAPK信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/318ada6961f8/12974_2015_349_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/48ac842a9319/12974_2015_349_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/22bab5141163/12974_2015_349_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/c1da27f33d55/12974_2015_349_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/7b02a24dbc39/12974_2015_349_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/318ada6961f8/12974_2015_349_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/48ac842a9319/12974_2015_349_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/22bab5141163/12974_2015_349_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/c1da27f33d55/12974_2015_349_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/7b02a24dbc39/12974_2015_349_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc7/4510892/318ada6961f8/12974_2015_349_Fig5_HTML.jpg

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