BLOCKADE OF N-TYPE AND Q-TYPE CA2-EVOKED [H-3] ACETYLCHOLINE-RELEASE IN RAT HIPPOCAMPAL SLICES( CHANNELS INHIBIT K+)

In the present study, we examined the contribution of specific Ca2+ ch annels to K+-evoked hippocampal acetylcholine (ACh) release using [H-3 ]choline loaded hippocampal slices. [H-3]ACh release was Ca2+-dependen t, blocked by the nonspecific Ca2+ channel blocker verapamil, but not by blockade of L-type Ca2+ channels, The N-type Ca2+ channel blocker o mega-conotoxin GVIA (omega-CgTx GVIA; 250 nM) inhibited [H-3]ACh relea se by 44% and the P/Q-type Ca2+ channel blocker omega-agatoxin IVA (om ega-Aga IVA; 400 nM) inhibited [H-3]ACh release by 27%, with the combi nation resulting in a nearly additive 79% inhibition, Four hundred or one thousand nM omega-Aga IVA was necessary to inhibit [H-3]ACh releas e. omega-Conotoxin MVIIC (omega-CTx-MVIIC) was used after first blocki ng N-type Ca2+ channels with omega-CgTx GVIA (1 mu M). Under these con ditions, 500 nM omega-CTx-MVIIC led to a nearly maximal inhibition of the omega-CgTx GVIA-insensitive [H-3]ACh release, Based on earlier rep orts about the relative sensitivity of cloned and native Ca2+ channels to these toxins, this study indicates that N- and Q-type Ca2+ channel s primarily mediate K+-evoked hippocampal [H-3]ACh release.