Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy.

Voltage-gated sodium channels (Na(V)) are critical for initiation of action potentials. Heterozygous loss-of-function mutations in Na(V)1.1 channels cause severe myoclonic epilepsy in infancy (SMEI). Homozygous null Scn1a-/- mice developed ataxia and died on postnatal day (P) 15 but could be sustained to P17.5 with manual feeding. Heterozygous Scn1a+/- mice had spontaneous seizures and sporadic deaths beginning after P21, with a notable dependence on genetic background. Loss of Na(V)1.1 did not change voltage-dependent activation or inactivation of sodium channels in hippocampal neurons. The sodium current density was, however, substantially reduced in inhibitory interneurons of Scn1a+/- and Scn1a-/- mice but not in their excitatory pyramidal neurons. An immunocytochemical survey also showed a specific upregulation of Na(V)1.3 channels in a subset of hippocampal interneurons. Our results indicate that reduced sodium currents in GABAergic inhibitory interneurons in Scn1a+/- heterozygotes may cause the hyperexcitability that leads to epilepsy in patients with SMEI.

Pubmed ID: 16921370


  • Yu FH
  • Mantegazza M
  • Westenbroek RE
  • Robbins CA
  • Kalume F
  • Burton KA
  • Spain WJ
  • McKnight GS
  • Scheuer T
  • Catterall WA


Nature neuroscience

Publication Data

September 28, 2006

Associated Grants


Mesh Terms

  • Action Potentials
  • Animals
  • Cell Line
  • Disease Models, Animal
  • Electroencephalography
  • Epilepsies, Myoclonic
  • Genotype
  • Humans
  • Immunoblotting
  • Infant
  • Interneurons
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mutation
  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • Patch-Clamp Techniques
  • Phenotype
  • Seizures
  • Sodium Channels
  • Survival Rate
  • gamma-Aminobutyric Acid