Voltage-sensitive calcium channel development in epileptic DBA/2J mice suggests altered presynaptic function

Epilepsia. 1994 Sep-Oct;35(5):911-4. doi: 10.1111/j.1528-1157.1994.tb02533.x.

Abstract

Aberrant synapse formation has been implicated in development and propagation of epileptic potential. Litzinger et al. (1993a) showed that omega-GVIA conotoxin may be used as a marker for synapse formation in nonepileptic mice. We conducted omega-GVIA binding in synaptosomal preparations from epileptic DBA/2J mice at different developmental ages. Binding in DBA/2J mice was compared with omega-GVIA binding in synaptosomal preparations from nonepileptic C57/B1, Swiss Webster, and AJ mice. Striking differences between these strains of mice are evident in the developmental sequence and pattern of N-type voltage-sensitive calcium channels (VSCC). In contrast to nonepileptic mice, the DBA/2J mice show a slow increase in omega-GVIA binding between postnatal days 2 and 8. This increase corresponds to onset of susceptibility to seizure in this strain. In addition to the difference in developmental sequence, DBA/2J mice have fewer binding sites for omega-GVIA throughout development, 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 presynaptic membranes responsible for neurotransmitter release may represent a change in synaptic activity that plays a role in epileptogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Brain / drug effects
  • Brain / growth & development*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Iodine Radioisotopes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mollusk Venoms
  • Peptides / pharmacology*
  • Seizures / genetics*
  • Synapses / drug effects
  • Synapses / metabolism*
  • omega-Conotoxins*

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Iodine Radioisotopes
  • Mollusk Venoms
  • Peptides
  • omega-Conotoxins
  • omega-conotoxin receptor
  • Conus magus toxin