The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum

1 The putative inhibitory effects of verapamil and diltiazem on neuronal non-L-type Ca2+ channels were studied by investigating their effects on either K-- or veratridine-evoked [H-3]-dopamine ([H-3]DA) release in rat striatal slices. Involvement of N-, P- and Q-type channels was identified by sensitivity of [3H]-DA release to omega-conotoxin GVIA (omega-CTx-GVIA), omega-agatoxin TVA (w-Aga-IVA) and omega-conotoxin MVIIC (omega-CTx-MVIIC). respectively. 2 KCl (50 mM)-evoked [3H]-DA release was abolished in the absence of Ca2+ , and was insensitive to dihydropyridines (up to 30 mu M). It was significantly blocked by w-CTx-GVIA (1 mu M), omega-Aga-IVA (30 nM) and was confirmed to be abolished by omega-CTx-MVIIC (3 mu M), indicating involvement of N-, P- and Q-type channel subtypes. 3 Verapamil and diltiazem inhibited K+-evoked [ H-3]-DA release in a concentration-dependent manner. The inhibitory effects of verapamil or diltiazem teach (30 mu M) were fully additive to the effect of omega-CTx-GVTA (1 mu M), whereas co-application with omega-Aga-IVA (30 n,M) produced similar effects to those of w-Aga-IVA alone. 4 As shown previously veratridine-evoked [H-3]-DA release in Ca2+ containing medium exclusively involves Q-type Ca2+ channels. Here, diltiazem (30 mu M) did not inhibit veratridine-evoked [H-3]-DA release? whereas verapamil (30 mu M) partially inhibited it, indicating possible involvement of Q-type channels in verapamil-induced inhibition. However, verapamil (30 mu M) inhibited this release even in the absence of extracellular Ca2+, suggesting that Na+ rather than Q-type Ca2+ channels are involved. 5 Taken together, our results suggest that verapamil can block P- and at higher concentrations possibly N- and Q-type Ca2+ channels linked to [H-3]-DA release, whereas diltiazem appears to block P-type Ca2+ channels only.