Neurotoxicity Research

, Volume 5, Issue 3, pp 213–219 | Cite as

Down-regulation of sodium channel Nav1.1 expression by veratridine and its reversal by a novel sodium channel blocker, RS100642, in primary neuronal cultures

  • Jitendra R. Dave
  • Changping Yao
  • John R. Moffett
  • Rossana Berti
  • Michael Koenig
  • Frank C. Tortella


This study investigated the effects of veratridine-induced neuronal toxicity on sodium channel gene (NaCh) expression in primary forebrain cultures enriched in neurons, and its reversal by a novel sodium channel blocker, RS100642. Using quantitative RTPCR, our findings demonstrated the expression ratio of NaCh genes in normal fetal rat forebrain neurons to be Nav1.2>Nav1.3>Nav1.8>Nav1.1>Nav1.7 (rBII>rBIII >PN3>rBI>PN1). Veratridine treatment of neuronal cells produced neurotoxicity in a dose-dependent manner (0.25−20 μM). Neuronal injury caused by a dose of veratridine producing 80% cell death (2.5 μM) significantly, and exclusively down-regulated the Nav1.1 gene. However, treatment of neurons with RS100642 (200 μM) reversed the down-regulation of the Nav1.1. gene expression caused by veratridine. Our findings document for the first time quantitative and relative changes in the expression of various NaCh genes in neurons following injury produced by selective activation of voltage-gated sodium channels, and suggest that the Nav1.1 sodium channel gene may play a key role in the neuronal injury/recovery process.


Veratridine Primary neuronal cultures Voltage-gated sodium channels Gene expression Quantitative RT-PCR 


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Copyright information

© FP Graham Publishing Co 2003

Authors and Affiliations

  • Jitendra R. Dave
    • 1
  • Changping Yao
    • 1
  • John R. Moffett
    • 1
  • Rossana Berti
    • 1
  • Michael Koenig
    • 2
  • Frank C. Tortella
    • 1
  1. 1.Department of Neuropharmacology and Molecular Biology, Division of Neurosciences, Rm. 2W14Walter Reed Army Institute of ResearchSilver SpringUSA
  2. 2.Department of Neuroendocrinology/Neurochemistry, Division of Neurosciences, Rm. 2W14Walter Reed Army Institute of ResearchSilver SpringUSA

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