Calcium channels involved in the inhibition of acetylcholine release by presynaptic muscarinic receptors in rat striatum

1 The mechanism of the inhibitory action of presynaptic muscarinic receptor s on the release of acetylcholine from striatal cholinergic neurons is not known. We investigated how the electrically stimulated release of [H-3]-ace tylcholine from superfused rat striatal slices and its inhibition by carbac hol are affected by specific inhibitors of voltage-operated calcium channel s of the L-type (nifedipine), N-type (omega-conotoxin GVIA) and P/Q-type (o mega-agatoxin IVA). 2 The evoked release of [H-3]-acetylcholine was not diminished by nifedipin e but was lowered by omega-conotoxin GVIA and by omega-agatoxin IVA, indica ting that both the N- and the P/Q-type (but not the L-tyge) channels are in volved in the release. The N-type channels were responsible for approximate ly two thirds of the release. The release was >97% blocked when both omega- toxins acted together. 3 The inhibition of [H-3]-acetylcholine release by carbachol was not substa ntially affected by the blockade of the L- or P/Q-type channels. It was dim inished but not eliminated by the blockade of the N-type channels. 4 In experiments on slices in which cholinesterases had been inhibited by p araoxon, inhibition of [JH]-acetylcholine release by endogenous acetylcholi ne accumulating in the tissue could be demonstrated by the enhancement of t he release after the addition of atropine. The inhibition was higher in sli ces with functional N-type than with functional P/Q-type channels. 5 We conclude that both the N- and the P/Q-type calcium channels contribute to the stimulation-evoked release of acetylcholine in rat striatum, that t he quantitative contribution of the N-type channels is higher, and that the inhibitory muscarinic receptors are more closely coupled with the N-type t han with the P/Q-type calcium channels.