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Nicotine‐evoked transmitter release from synaptosomes: functional association of specific presynaptic acetylcholine receptors and voltage‐gated calcium channels
Author(s) -
Kulak Jennifer M.,
McIntosh J. Michael,
Yoshikami Doju,
Olivera Baldomero M.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00357.x
Subject(s) - voltage dependent calcium channel , nicotinic agonist , dopamine , chemistry , nicotine , synaptosome , calcium channel , t type calcium channel , calcium , p type calcium channel , acetylcholine receptor , neurotransmitter , biophysics , endocrinology , medicine , neuroscience , receptor , biology , biochemistry , organic chemistry
It has previously been shown that nicotine‐evoked dopamine release from rat striatal synaptosomes and nicotine‐evoked norepinephrine release from hippocampal synaptosomes are mediated by distinct nicotinic acetylcholine receptor (nAChR) subtypes. In the present study, the functional association of these nicotinic receptors with specific subtypes of voltage‐gated calcium channels was examined. Cd 2+ (200 µ m ), as well as ω‐conotoxin MVIIC (5 µ m ), blocks ∼85% of nicotine‐evoked dopamine release from striatal synaptosomes, indicating a major involvement of calcium channels. Furthermore, the toxin‐susceptibility suggests that these calcium channels contain α 1A and/or α 1B subunits. Inhibition of nicotine‐evoked dopamine release by conotoxins α‐MII and ω‐GVIA is additive and indicates that presynaptic α3β2 nAChRs are functionally coupled to α 1A , but not α 1B , calcium channel subtypes. Conversely, insensitivity to α‐AuIB and sensitivity to ω‐MVIIC indicate that non‐α3β2/α3β4‐containing nAChRs are functionally coupled to α 1B ‐containing calcium channels. In contrast, Cd 2+ blocks only 65% of nicotine‐evoked norepinephrine release from hippocampal synaptosomes, indicating that a substantial fraction of this release occurs through mechanisms not involving calcium channels. This Cd 2+ ‐insensitive component of release is blocked by α‐AuIB and therefore appears to be triggered by Ca 2+ flowing directly through the channels of presynaptic α3β4 nAChRs. Thus, these data indicate that different presynaptic termini can have distinctive functional associations of specific nAChRs and voltage‐gated calcium channels.