Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy

Joshua P. Klein, Davender S. Khera, Hrachya Nersesyan, Eyal Y. Kimchi, Stephen G. Waxman, Hal Blumenfeld*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Due to the involvement of cortical neurons in spike-wave discharge (SWD) initiation, and the contribution of voltage-gated sodium channels (VGSCs) to neuronal firing, we examined alterations in the expression of VGSC mRNA and protein in cortical neurons in the WAG/Rij absence epileptic rat. WAG/Rij rats were compared to age-matched Wistar control rats at 2, 4, and 6 months. Continuous EEG data was recorded, and percent time in SWD was determined. Tissue from different cortical locations from WAG/Rij and Wistar rats was analyzed for VGSC mRNA (by quantitative PCR) and protein (by immunocytochemistry). SWDs increased with age in WAG/Rij rats. mRNA levels for sodium channels Nav1.1 and Nav1.6, but not Nav1.2, were found to be up-regulated selectively within the facial somatosensory cortex (at AP +0.0, ML +6.0 mm). Protein levels for Nav1.1 and Nav1.6 were up-regulated in layer II-IV cortical neurons in this region of cortex. No significant changes were seen in adjacent regions or other brain areas, including the pre-frontal and occipital cortex. In the WAG/Rij model of absence epilepsy, we identified a specific region of cortex, in layer II-IV neurons on the lateral convexity of the cortex in the facial somatosensory area, where mRNA and protein expression of sodium channel genes Nav1.1 and Nav1.6 are up-regulated. This region of cortex approximately matches the electrophysiologically determined region of seizure onset. Changes in the expression of Nav1.1 and Nav1.6 parallel age-dependent increases in seizure frequency and duration.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalBrain research
Issue number1-2
StatePublished - Mar 12 2004


  • Burst firing
  • Disorders of the nervous system
  • Epilepsy: human studies and animal models
  • Hyperexcitability
  • Ion channel
  • Persistent current
  • Spike-wave seizure
  • WAG/Rij

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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