title: Nicotine-evoked transmitter release from synaptosomes: functional association of specific presynaptic acetylcholine receptors and voltage-gated calcium channels.
abstract: 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 microM), as well as omega-conotoxin MVIIC (5 microM), blocks approximately 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 alpha(1A) and/or alpha(1B) subunits. Inhibition of nicotine-evoked dopamine release by conotoxins alpha-MII and omega-GVIA is additive and indicates that presynaptic alpha3beta2 nAChRs are functionally coupled to alpha(1A), but not alpha(1B), calcium channel subtypes. Conversely, insensitivity to alpha-AuIB and sensitivity to omega-MVIIC indicate that non-alpha3beta2/alpha3beta4-containing nAChRs are functionally coupled to alpha(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 alpha-AuIB and therefore appears to be triggered by Ca(2+) flowing directly through the channels of presynaptic alpha3beta4 nAChRs. Thus, these data indicate that different presynaptic termini can have distinctive functional associations of specific nAChRs and voltage-gated calcium channels.
authors: Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah 84112-0840, USA.
authors: J M
authors: JM
authors: Kulak
authors: J M
authors: JM
authors: McIntosh
authors: D
authors: D
authors: Yoshikami
authors: B M
authors: BM
authors: Olivera
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020916:Conotoxins / Q000494:pharmacology; D004298:Dopamine / Q000493:pharmacokinetics; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020916:Conotoxins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; C098872:alpha-conotoxin MII; C419362:nicotinic receptor alpha3beta2; D020960:omega-Conotoxins; D002104:Cadmium; D014316:Tritium; C075851:omega-conotoxin-MVIIC; D009538:Nicotine; D020866:omega-Conotoxin GVIA; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine