Blockade of N- and Q-type Ca super(2+) channels inhibit K super(+)-evoked [ super(3)H]acetylcholine release in rat hippocampal slices

In the present study, we examined the contribution of specific Ca super(2+) channels to K super(+)-evoked hippocampal acetylcholine (ACh) release using [ super(3)H]choline loaded hippocampal slices. [ super(3)H]ACh release was Ca super(2+)-dependent, blocked by the nonspecific Ca super(2+) channel blocker verapamil, but not by blockade of L-type Ca super(2+) channels. The N-type Ca super(2+) channel blocker omega -conotoxin GVIA ( omega -CgTx GVIA; 250 nM) inhibited [ super(3)H]ACh release by 44% and the P/Q-type Ca super(2+) channel blocker omega -agatoxin IVA ( omega -Aga IVA; 400 nM) inhibited [ super(3)H]ACh release by 27%, with the combination resulting in a nearly additive 79% inhibition. Four hundred or one thousand nM omega -Aga IVA was necessary to inhibit [ super(3)H]ACh release. omega -Conotoxin MVIIC ( omega -CTx-MVIIC) was used after first blocking N-type Ca super(2+) channels with omega -CgTx GVIA (1 mu M). Under these conditions, 500 nM omega -CTx-MVIIC led to a nearly maximal inhibition of the omega -CgTx GVIA-insensitive [ super(3)H]ACh release. Based on earlier reports about the relative sensitivity of cloned and native Ca super(2+) channels to these toxins, this study indicates that N- and Q-type Ca super(2+) channels primarily mediate K super(+)-evoked hippocampal [ super(3)H]ACh release.