Mutations in SCN1A, the gene encoding NaV1.1 sodium channels, cause a spectrum of epilepsy disorders that range from genetic epilepsy with febrile seizures plus (GEFS+) to catastrophic disorders like Dravet Syndrome (DS). To date, more than 1250 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. Here 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 iPSC-derived neurons.
- model systems
- Copyright © 2015, Journal of Neurophysiology