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Calcium mobilization elicited by two types of nicotinic acetylcholine receptors in mouse substantia nigra pars compacta
Author(s) -
Tsuneki Hiroshi,
Klink Ruby,
Léna Clément,
Korn Henri,
Changeux JeanPierre
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00138.x
Subject(s) - methyllycaconitine , substantia nigra , pars compacta , chemistry , nicotinic agonist , nicotine , acetylcholine , nicotinic acetylcholine receptor , endocrinology , acetylcholine receptor , nicotinic antagonist , medicine , pharmacology , dopaminergic , receptor , biology , dopamine , biochemistry
Nicotinic acetylcholine receptors (nAChRs) are expressed in the midbrain ascending dopaminergic system, a target of many addictive drugs. Here we assessed the intracellular Ca 2+ level by imaging fura‐2‐loaded cells in substantia nigra pars compacta in mouse brain slices, and we examined the influence on this level of prolonged exposures to nicotine using mice lacking the nAChR β2‐subunit. In control cells, superfusion with nicotine (10–100 μ m ) caused a long‐lasting rise of intracellular Ca 2+ level which depended on extracellular Ca 2+ . This nicotinic response was almost completely absent in β2–/– mutant mice, leaving a small residual response to a high concentration (100 μ m ) of nicotine which was inhibited by the α7‐subunit‐selective antagonist, methyllycaconitine. Conversely, the α7‐subunit‐selective agonist choline (10 m m ) caused a methyllycaconitine‐sensitive increase in intracellular Ca 2+ level both in wild‐type and β2–/– mutant mice. Nicotine‐elicited Ca 2+ mobilization was reduced by the Na + channel blocker tetrodotoxin (TTX) and by T‐type Ca 2+ channel blocking agents, whereas the choline‐elicited Ca 2+ increase was insensitive to TTX. Neither nicotine nor choline produced Ca 2+ increase following inhibition of the release of Ca 2+ from intracellular stores by dantrolene. These results demonstrate that in nigral dopaminergic neurons, nicotine can elicit Ca 2+ mobilization via activation of two distinct nAChR subtypes: that of β2‐subunit‐containing nAChR followed by activation of Na + channel and T‐type Ca 2+ channels, and/or activation of α7‐subunit‐containing nAChR. The Ca 2+ influx due to nAChR activation is subsequently amplified by the recruitment of intracellular Ca 2+ stores. This Ca 2+ mobilization may possibly contribute to the long‐term effects of nicotine on the dopaminergic system.