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

Frank H. Yu, Massimo Mantegazza, Ruth E. Westenbroek, Carol A. Robbins, Franck Kalume, Kimberly A. Burton, William J. Spain, G. Stanley McKnight, Todd Scheuer, William A. Catterall

Research output: Contribution to journalArticlepeer-review

Abstract

Voltage-gated sodium channels (NaV) are critical for initiation of action potentials. Heterozygous loss-of-function mutations in Na V1.1 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 V1.1 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 V1.3 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.

Original languageEnglish
Pages (from-to)1142-1149
Number of pages8
JournalNature Neuroscience
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 2006

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy'. Together they form a unique fingerprint.

Cite this