Molecular basis of an inherited epilepsy

Christoph Lossin, Dao W. Wang, Thomas H. Rhodes, Carlos G. Vanoye, Alfred L. George*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

287 Scopus citations

Abstract

Epilepsy is a common neurological condition that reflects neuronal hyperexcitability arising from largely unknown cellular and molecular mechanisms. In generalized epilepsy with febrile seizures plus, an autosomal dominant epilepsy syndrome, mutations in three genes coding for voltage-gated sodium channel α or β1 subunits (SCN1A, SCN2A, SCN1B) and one GABA receptor subunit gene (GABRG2) have been identified. Here, we characterize the functional effects of three mutations in the human neuronal sodium channel α subunit SCN1A by heterologous expression with its known accessory subunits, β1 and β2, in cultured mammalian cells. SCN1A mutations alter channel inactivation, resulting in persistent inward sodium current. This gain-of-function abnormality will likely enhance excitability of neuronal membranes by causing prolonged membrane depolarization, a plausible underlying biophysical mechanism responsible for this inherited human epilepsy.

Original languageEnglish (US)
Article numberS0896-6273(02)00714-6
Pages (from-to)877-884
Number of pages8
JournalNeuron
Volume34
Issue number6
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Neuroscience(all)

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