Modulation of nicotine-evoked [3H]dopamine release from rat striatal synaptosomes by voltage-sensitive calcium channel ligands.

The calcium channel subtypes mediating nicotine-evoked [3H]dopamine release from rat striatal synaptosomes were probed with L-, N-, and P-type calcium channel ligands. Responses to nicotine were blocked by the peptides omega-conotoxin GVIA and omega-agatoxin IVA. The affinity constants for these compounds were consistent with their actions at N- and P-type channels, respectively. Together, these channels mediate at least 90% of the calcium-dependent response to nicotine. The L-type antagonists nifedipine, verapamil, and nicardipine were also effective blockers of nicotine-evoked release with maximal effects of 80-100% inhibition. However, these effects occurred at concentrations 2-3 orders of magnitude higher than those necessary to block L-type channels. Moreover, Bay K8644, an L-type agonist, also blocked nicotine-evoked release. Together, these findings argue strongly against the involvement of L-type channels.