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

Brain Res. 2004 Mar 12;1000(1-2):102-9. doi: 10.1016/j.brainres.2003.11.051.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Aging / genetics
  • Aging / physiology
  • Animals
  • Cerebral Cortex / metabolism*
  • Disease Models, Animal*
  • Epilepsy, Absence / genetics
  • Epilepsy, Absence / metabolism*
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Neurons / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Sodium Channels / biosynthesis*
  • Sodium Channels / genetics
  • Up-Regulation / physiology*


  • Nerve Tissue Proteins
  • RNA, Messenger
  • Sodium Channels