Model systems for studying cellular mechanisms of SCN1A-related epilepsy

J Neurophysiol. 2016 Apr;115(4):1755-66. doi: 10.1152/jn.00824.2015. Epub 2016 Feb 3.


Mutations in SCN1A, the gene encoding voltage-gated sodium channel NaV1.1, cause a spectrum of epilepsy disorders that range from genetic epilepsy with febrile seizures plus to catastrophic disorders such as Dravet syndrome. To date, more than 1,250 mutations in SCN1A have been linked to epilepsy. Distinct effects of individual SCN1A mutations on neuronal function are likely to contribute to variation in disease severity and response to treatment in patients. Several model systems have been used to explore seizure genesis in SCN1A epilepsies. In this article we review what has been learned about cellular mechanisms and potential new therapies from these model systems, with a particular emphasis on the novel model system of knock in Drosophila and a look toward the future with expanded use of patient-specific induced pluripotent stem cell-derived neurons.

Keywords: Drosophila; SCN1A; epilepsy; iPSC; model systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drosophila / genetics
  • Epilepsy / genetics
  • Epilepsy / metabolism*
  • Humans
  • Mutation*
  • NAV1.1 Voltage-Gated Sodium Channel / genetics
  • NAV1.1 Voltage-Gated Sodium Channel / metabolism*


  • NAV1.1 Voltage-Gated Sodium Channel