N-type calcium channels are involved in the dopamine releasing effect of nicotine

Abstract

Mouse striatum was incubated with [3H]dopamine ([3H]DA) and superfused with and the tritium efflux induced by nicotine, electrical stimulation, or simultaneous nicotine and electrical stimulation was measured, to characterize the role of different Ca2+ channels in the transmitter release. Nicotine stimulation and electrical stimulation exerted additive effects on tritium efflux. Separation of the released radioactivity on alumina columns indicated that nicotine or electrical stimulation increases the release of [3H]DA and that the outflow of 3H-labeled metabolites was similar with the two different stimulation procedures. Removal of Ca2+ from the superfusate resulted in a marked reduction in the tritium release evoked by nicotine, whereas the electrical stimulation-evoked tritium release was completely dependent on external Ca2+. The L- and N-type calcium channel blockers omega-conotoxin GVIA and Cd2+ inhibited the tritium release from the striatum evoked by either nicotine or electrical stimulation, whereas the L-type and T-type channel blockers diltiazem and Ni2+ did not alter release of [3H]DA. We conclude that N-type voltage-sensitive Ca2+ channels participate in striatal dopamine release, and we speculate that nicotinic receptor-operated ion channels permeable to cations such as Ca2+ and N-type voltage-sensitive calcium channels may simultaneously open up, and they additively increase free intracellular Ca2+ concentration.

Effects of the calcium channel blocker nimodipine on nicotine-induced locomotion in rats

“…Because there exists a general consensus that mesolimbic dopaminergic transmission underlies nicotine-induced locomotion, dopamine is the likely neurotransmitter candidate (Clarke et al 1988). However, our findings appear to be in some conflict with those recently reported by Harsing et al (1992). They concluded that nicotine-induced dopamine release in the striatum is mediated by the N-type calcium channel.…”

“…There is evidence that suggests both the L-and N-type calcium channels play a role in the release of dopamine induced by drugs of abuse (Pani et al 1990;Harsing et al 1992). Pani et al (1990) found that cocaine-induced dopamine release is blocked by L-type calcium channel blockers, whereas Harsing et al (1992) reported that dopamine release by nicotine is attenuated by omega-conotoxin, an N-type calcium channel antagonist.…”

“…The L-and N-type are thought to play a dominant role in calcium dependent neurotransmitter release, whereas the T-type is only thought to participate indirectly in neurotransmitter release (Hirning et al 1988;Kato et al 1992). There is evidence that suggests both the L-and N-type calcium channels play a role in the release of dopamine induced by drugs of abuse (Pani et al 1990;Harsing et al 1992). Pani et al (1990) found that cocaine-induced dopamine release is blocked by L-type calcium channel blockers, whereas Harsing et al (1992) reported that dopamine release by nicotine is attenuated by omega-conotoxin, an N-type calcium channel antagonist.…”

Domain III regulates N-type (CaV2.2) calcium channel closing kinetics

“…Clinical relevance of slowed deactivation. Ca V 2 channels are localized within nerve terminals in both the central and peripheral nervous systems and serve as the major pathway for Ca 2ϩ entry that triggers neurotransmitter release (Harsing et al 1992;Hirning et al 1988;Shimosawa et al 2004;Wheeler et al 1994). Until the identification of R-roscovitine, there were no drugs available to enhance Ca 2ϩ influx through presynaptic Ca V 2 channels (Buraei et al 2005(Buraei et al , 2007Yan et al 2002).…”

Handbook of Neurochemistry and Molecular Neurobiology

“…As a consequence of the enhanced free intracellular Ca 2þ , an exocytotic process may trigger dopamine release from vesicular pool. In many experimental conditions, dopamine release evoked by nicotine has been reported to be partly external Ca 2þ -dependent (Harsing et al, 1992).…”