EFFECTS OF L-TYPE AND N-TYPE CA2+ CHANNEL ANTAGONISTS ON EXCITATORY AMINO ACID-EVOKED DOPAMINE RELEASE

In the present study we tested the effect of dihydropyridine (DHP) Ca2+ channel antagonists and of omega-conotoxin GVIA on [H-3]dopamine (DA) release evoked by the activation of excitatory amino acid (EAA) receptors in cultures of fetal rat ventral mesencephalon, in order to investigate the role of voltage-sensitive L- and N-type Ca2+ channels in these EAA-mediated processes. Micromolar concentrations (10-30 muM) of DHP L-type Ca2+ channel antagonists inhibited [H-3]DA release evoked by N-methyl-D-aspartate (NMDA), kainate, quisqualate or veratridine. [H-3]DA release evoked by the L-type Ca2+ channel agonist, Bay K 8644, was inhibited by lower concentrations (0.1-1 muM) of the DHP antagonist, nitrendipine, than was the release evoked by EAAs. The DHP antagonist, (+)-PN 200-110, was more potent than (-)-PN 200-110 in inhibiting [H-3]DA release evoked by Bay K 8644, but the two stereoisomers were equipotent in inhibiting NMDA-evoked release. These results indicate that activation of L-type Ca2+ channels is able to evoke [H-3]DA release. However activation of L-type channels is not involved in EAA-induced [H-3]DA release and therefore inhibition of EAA-induced [H-3]DA release by micromolar concentrations of DHPs must bc mediated by actions other than inhibition of L-type Ca2+ channels. Omega-conotoxin GVIA (3 muM) had no effect on [H-3]DA release evoked by Bay K 8644, indicating that the toxin may selectively inhibit N-type channels in this preparation. Omega-conotoxin GVIA (3 muM) partially inhibited [H-3]DA release evoked by NMDA or kainate, suggesting that N-type Ca2+ channels could possibly play a role in EAA-mediated responses in these cells.