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

The putative inhibitory effects of verapamil and diltiazem on neuronal non‐L‐type Ca 2+ channels were studied by investigating their effects on either K + ‐ or veratridine‐evoked [ 3 H]‐dopamine ([ 3 H]‐DA) release in rat striatal slices. Involvement of N‐, P‐ and Q‐type channels was identified by sensitivity of [ 3 H]‐DA release to ω‐conotoxin GVIA (ω‐CTx‐GVIA), ω‐agatoxin IVA (ω‐Aga‐IVA) and ω‐conotoxin MVIIC (ω‐CTx‐MVIIC), respectively. KCl (50 m M )‐evoked [ 3 H]‐DA release was abolished in the absence of Ca 2+ , and was insensitive to dihydropyridines (up to 30 μ M ). It was significantly blocked by ω‐CTx‐GVIA (1 μ M ), ω‐Aga‐IVA (30 n M ) and was confirmed to be abolished by ω‐CTx‐MVIIC (3 μ M ), indicating involvement of N‐, P‐ and Q‐type channel subtypes. Verapamil and diltiazem inhibited K + ‐evoked [ 3 H]‐DA release in a concentration‐dependent manner. The inhibitory effects of verapamil or diltiazem (each 30 μ M ) were fully additive to the effect of ω‐CTx‐GVIA (1 μ M ), whereas co‐application with ω‐Aga‐IVA (30 n M ) produced similar effects to those of ω‐Aga‐IVA alone. As shown previously, veratridine‐evoked [ 3 H]‐DA release in Ca 2+ containing medium exclusively involves Q‐type Ca 2+ channels. Here, diltiazem (30 μ M ) did not inhibit veratridine‐evoked [ 3 H]‐DA release, whereas verapamil (30 μ M ) partially inhibited it, indicating possible involvement of Q‐type channels in verapamil‐induced inhibition. However, verapamil (30 μ M ) inhibited this release even in the absence of extracellular Ca 2+ , suggesting that Na + rather than Q‐type Ca 2+ channels are involved. Taken together, our results suggest that verapamil can block P‐ and at higher concentrations possibly N‐ and Q‐type Ca 2+ channels linked to [ 3 H]‐DA release, whereas diltiazem appears to block P‐type Ca 2+ channels only.British Journal of Pharmacology (1999) 127 , 576–582; doi: 10.1038/sj.bjp.0702574