Modulation of potassium-evoked [3H]dopamine release from rat striatal slices by voltage-activated calcium channel ligands: effects of omega-conotoxin-MVIIC.

Abstract

We examined the involvement of voltage-activated Ca2+ channels (VACCs) on K+(50 mM)-evoked [3H]dopamine ([3H]DA) release from superfused rat striatal slices. Neither nifedipine nor nitrendipine modified K(+)-evoked [3H]DA release, indicating that L-type VACCs are not involved. K(+)-evoked [3H]DA release was partially inhibited by omega-CTx-GVIA and omega-Aga-IVA, and was abolished by 3 microM omega-CTx-MVIIC (IC50 approximately 128 nM), suggesting the involvement of N-, P-, or Q-type VACCs, respectively. Moreover, even subnanomolar concentrations of omega-CTx-MVIIC (0.1-0.5 nM) inhibited K(+)-evoked [3H]DA release by approximately 25%, suggesting the possible involvement of a still not classified (perhaps O-type?) Ca2+ channel subtype. The effects of omega-CTx-MVIIC (10-100 nM) and omega-CTx-GVIA (1 microM) were additive, suggesting that low nanomolar concentrations of omega-CTx-MVIIC does not interact with N-type VACCs. In conclusion, the K(+)-evoked [3H]DA release from rat striatal slices is mediated by entry of Ca2+ through omega-CTx-GVIA sensitive (N-type) as well as through omega-Aga-IVA (P-type) and omega-CTx-MVIIC (probably Q-type) sensitive VACCs.