Inhibition of N-methyl-D-aspartate- and kainic acid-induced neurotransmitter release by ω-conotoxin GVIA

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Abstract
1 The role of voltage-sensitive calcium channels (VSCC) in N-methyl-D-aspartate (NMDA)- and kainic acid (KA)-evoked neurotransmitter release from rat cortical and hippocampal brain slices was evaluated by determining the effects of ω-conotoxin GVIA, an inhibitor of neuronal L- and N-type VSCC, and PN 200–110, a selective inhibitor of L-type VSCC. 2 Selective antagonists of the NMDA receptor ionophore complex, Mg2+, CPP and MK-801, inhibited NMDA- but not KA-evoked release of [3H]-noradrenaline from hippocampal and cortical brain slices. This suggests that cortical and hippocampal receptors are similar and that NMDA and KA act at distinct excitatory amino acid receptor subtypes. 3 [3H]-noradrenaline release induced by both NMDA and KA was similarly inhibited (approximately 30%) by ω-conotoxin GVIA. In contrast, PN 200–110 had no significant effect, although there was a tendency towards inhibition. 4 The results suggest that although NMDA- and KA-receptors are pharmacologically distinct, the N-type, but not the L-type, VSCC plays a small but significant role in neurotransmitter release induced by both NMDA and KA. It remains to be determined whether the N-type VSCC are involved in the physiological and/or pathological manifestations of excitatory amino acid receptor stimulation.
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