Inhibition of central neurotransmitter release by omega-conotoxin GVIA, a peptide modulator of the N-type voltage-sensitive calcium channel.

Tritium overflows, evoked by electrical stimulation (2 min; 2 ms, 3 Hz, 5 V/cm, and 24 mA) of [3H]-dopamine-, [3H]-noradrenaline-, [3H]-5-hydroxytryptamine, and [3H]-acetylcholine-labeled slices prepared from discrete regions of the rabbit central nervous system, were inhibited 39-50% by omega-conotoxin GVIA (omega-CT; 5 nmol/l), a peptide modulator of the N-type voltage-sensitive calcium channel (N-VSCC). Additional experiments using omega-CT (5 nmol/l) and [3H]-noradrenaline-labeled hippocampal slices indicated the time dependence of omega-CT-induced inhibition, the competitive antagonism between buffer calcium concentration and omega-CT, and the lack of effect of prolonged electrical stimulation (15 min; 0.4 Hz) on omega-CT-induced inhibition. These various results suggest that 1) omega-CT competes with calcium for the N-VSCC, 2) the inhibitory effects of omega-CT are independent of the gating state of the N-VSCC, and 3) the molecular nature of the N-VSCC may be similar or identical across central neurotransmitter systems. omega-CT appears to be a useful pharmacological tool in studying the involvement of the N-VSCC in neurotransmitter release.