VOLTAGE-SENSITIVE CALCIUM-CHANNEL DEVELOPMENT IN EPILEPTIC DBA 2J MICE SUGGESTS ALTERED PRESYNAPTIC FUNCTION/

Aberrant synapse formation has been implicated in development and prop agation of epileptic potential. Litzinger et al. (1993a) showed that o mega-GVIA conotoxin may be used as a marker for synapse formation in n onepileptic mice. We conducted omega-GVIA binding in synaptosomal prep arations from epileptic DBA/2J mice at different developmental ages. B inding in DBA/2J mice was compared with omega-GVIA binding in synaptos omal preparations from nonepileptic C57/B1, Swiss Webster, and AJ mice . Striking differences between these strains of mice are evident in th e developmental sequence and pattern of N-type voltage:sensitive calci um channels (VSCC). In contrast to nonepileptic mice, the DBA/2J mice show a slow increase in omega-GVIA binding between postnatal days 2 an d 8. This increase corresponds to onset of susceptibility to seizure i n this strain. In addition to the difference in developmental sequence , DBA/2J mice have fewer binding sites for omega-GVIA throughout devel opment, suggesting changes in channel structure or number. These data show that in DBA/2J mice development of the VSCC in brain is different from that in nonepileptic mice. This difference in development in pre synaptic membranes responsible for neurotransmitter release may repres ent a change in synaptic activity that plays a role in epileptogenesis .