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

Abstract

1 The mechanism of the inhibitory action of presynaptic muscarinic receptors on the release of acetylcholine from striatal cholinergic neurons is not known. We investigated how the electrically stimulated release of [ 3 H]-acetylcholine from superfused rat striatal slices and its inhibition by carbachol are aected by speci®c inhibitors of voltage-operated calcium channels of the L-type (nifedipine), N-type (o-conotoxin GVIA) and P/Q-type (o-agatoxin IVA). 2 The evoked release of [ 3 H]-acetylcholine was not diminished by nifedipine but was lowered by oconotoxin GVIA and by o-agatoxin IVA, indicating that both the N-and the P/Q-type (but not the L-type) channels are involved in the release. The N-type channels were responsible for approximately two thirds of the release. The release was 497% blocked when both o-toxins acted together.3 The inhibition of [ 3 H]-acetylcholine release by carbachol was not substantially aected by the blockade of the L-or P/Q-type channels. It was diminished but not eliminated by the blockade of the N-type channels. 4 In experiments on slices in which cholinesterases had been inhibited by paraoxon, inhibition of [ 3 H]-acetylcholine release by endogenous acetylcholine accumulating in the tissue could be demonstrated by the enhancement of the release after the addition of atropine. The inhibition was higher in slices 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 stimulationevoked release of acetylcholine in rat striatum, that the quantitative contribution of the N-type channels is higher, and that the inhibitory muscarinic receptors are more closely coupled with the Ntype than with the P/Q-type calcium channels.

Selective Blockade of N‐Type Calcium Channels by Levetiracetam

“…At the same time, this also may explain the specific binding of LEV in rat central nervous system (CNS) (40), where N‐type channels (α1B) are principally expressed in comparison with other tissues (41). The predominant action of LEV on discrete areas of rat brain such as striatum (42), where N‐type channels compose the main subpopulation of calcium channels (43), was shown. It also was shown that another AED, lamotrigine (LTG; Lamictal) also can exert its effect through inhibition of presynaptic N‐type Ca 2+ channels (44–46).…”

Postnatal development of cholinergic synapses on mouse spinal motoneurons

“…In central neurons, evoked vesicular release of ACh is dependent on calcium entry into the presynaptic terminal through voltage‐gated calcium channels (Dolezal and Tucek, 1999). Ca V 2.2 channels have been demonstrated in cholinergic terminals on adult rat myenteric neurons (Kirchgessner and Liu, 1999).…”

Natural Peptides in Drug Discovery Targeting Acetylcholinesterase

“…The inhibition was high in slices with functional N-type channels. Thus, it was concluded that the N-type calcium channel may contribute to the stimulation of acetylcholine release in rat striatum [ 97 ].…”