title: Tumor necrosis factor-α enhances voltage-gated Na⁺ currents in primary culture of mouse cortical neurons.
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.
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, , Guangdong, China. wqchen@stu.edu.cn.|Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, 515041, , Guangdong, China. wqchen@stu.edu.cn.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, , Guangdong, China. shengfuyou@yeah.net.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, 515041, , Guangdong, China. guojf13688@126.com.
authors.forename: Jingfang
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, , Guangdong, China. ffgao@stu.edu.cn.
authors.forename: Fenfei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, , Guangdong, China. 2425952673@qq.com.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, , Guangdong, China. daijpedu2008@163.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, , Guangdong, China. gefeiwang@stu.edu.cn.
authors.forename: Gefei
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, , Guangdong, China. ksli2013@yeah.net.
authors.forename: Kangsheng
authors.initials: K
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016328:NF-kappa B / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000187:drug effects* / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D007093:Imidazoles; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D061566:Voltage-Gated Sodium Channels; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580