Blockade of N- and Q-type Ca2+ channels inhibit K(+)-evoked [3H]acetylcholine release in rat hippocampal slices.

In the present study, we examined the contribution of specific Ca2+ channels to K(+)-evoked hippocampal acetylcholine (ACh) release using [3H]choline loaded hippocampal slices. [3H]ACh release was Ca(2+)-dependent, blocked by the nonspecific Ca2+ channel blocker verapamil, but not by blockade of L-type Ca2+ channels. The N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CgTx GVIA; 250 nM) inhibited [3H]ACh release by 44% and the P/Q-type Ca2+ channel blocker omega-agatoxin IVA (omega-Aga IVA; 400 nM) inhibited [3H]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 [3H]ACh release. omega-Conotoxin MVIIC (omega-CTx-MVIIC) was used after first blocking N-type Ca2+ channels with omega-CgTx GVIA (1 microM). Under these conditions, 500 nM omega-CTx-MVIIC led to a nearly maximal inhibition of the omega-CgTx GVIA-insensitive [3H]ACh release. Based on earlier reports about the relative sensitivity of cloned and native Ca2+ channels to these toxins, this study indicates that N- and Q-type Ca2+ channels primarily mediate K(+)-evoked hippocampal [3H]ACh release.