Voltage-sensitive calcium channel development in epileptic DBA/2J mice suggests altered presynaptic function.
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.
Esplin
M S
MS
Department of Pediatrics, University of Utah, Salt Lake City 84132.
Abbott
J R
JR
Smart
M L
ML
Burroughs
A F
AF
Frandsen
T C
TC
Litzinger
M J
MJ
D000161:Acoustic Stimulation; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008978:Mollusk Venoms; D010455:Peptides / Q000494:pharmacology*; D012640:Seizures / Q000235:genetics*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007457:Iodine Radioisotopes; D008978:Mollusk Venoms; D010455:Peptides; D020960:omega-Conotoxins; C053157:omega-conotoxin receptor; C053423:Conus magus toxin