The voltage-sensitive Ca2+ channel (VSCC) antagonists omega-Aga-IVA and omega-CTX-MVIIC inhibit spontaneous epileptiform discharges in the rat cortical wedge.
The ability of VSCC antagonists to modulate excitatory amino acid (EAA) release was evaluated by measuring N-methyl-D-aspartate (NMDA) receptor-dependent spontaneous epileptiform discharges in rat cortical wedges. The N-type channel blocker omega-CTX-GVIA (300 nM) was ineffective. The P-type channel blocker omega-Aga-IVA at 300 nM reduced the frequency of discharges by 63%, while 300 nM omega-CTX-MVIIC reduced the frequency by 35%. These results coupled with the absence of NMDA antagonism by omega-Aga-IVA or omega-CTX-MVIIC in the cortical wedge suggest that the VSCCs blocked by these toxins are primarily responsible for mediating impulse dependent EAA release in the rat neocortex.
Robichaud
L J
LJ
Department of Neuroscience Pharmacology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105.
Wurster
S
S
Boxer
P A
PA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D004594:Electrophysiology / Q000379:methods; D004827:Epilepsy; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013111:Spider Venoms / Q000494:pharmacology*; D013997:Time Factors; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D010455:Peptides; D016194:Receptors, N-Methyl-D-Aspartate; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC