[PDF][PDF] Molecular basis of an inherited epilepsy

C Lossin, DW Wang, TH Rhodes, CG Vanoye… - Neuron, 2002 - cell.com
C Lossin, DW Wang, TH Rhodes, CG Vanoye, AL George
Neuron, 2002cell.com
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 …
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.
cell.com