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.
Department of Neuroscience Pharmacology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105.
L J
LJ
Robichaud
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S
Wurster
P A
PA
Boxer
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