Sodium channels splicing and seizure susceptibility
Category: Current
Published Date
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Clinical data have identified connection of a L1563V mutation in the SCN2A protein (a sodium channel protein) to childhood epilepsy. The SCN2A protein has 2 isoforms, neonatal and adult. Our data has shown that when expressed in HEK293 cells, the neonatal channel is less excitable than the adult form, and the L1563V mutation of the mutant form results in an increase in excitability to adult protein levels. Our hypothesis is, therefore, that alternative splicing may be critical in reducing excitability in the infantile brain and susceptibility to seizures. We are currently genetically engineering mutant mice with permanent "neonatal" or "adult" SCN2A genes to test this hypothesis and clarify the developmental roles of these isoforms.
