Nicotine-evoked transmitter release from synaptosomes: functional association of specific presynaptic acetylcholine receptors and voltage-gated calcium channels

It has previously been shown that nicotine-evoked dopamine release from rat striatal synaptosomes and nicotine-evoked norepinephrine release from hipp ocampal synaptosomes are mediated by distinct nicotinic acetylcholine recep tor (nAChR) subtypes. In the present study, the functional association of t hese nicotinic receptors with specific subtypes of voltage-gated calcium ch annels was examined. Cd2+ (200 muM), as well as omega -conotoxin MVIIC (5 m uM), blocks similar to 85% of nicotine-evoked dopamine release from striata l synaptosomes, indicating a major involvement of calcium channels. Further more, the toxin-susceptibility suggests that these calcium channels contain alpha (1A) and/or alpha (1B) subunits. Inhibition of nicotine-evoked dopam ine release by conotoxins a-MII and omega -GVIA is additive and indicates t hat presynaptic alpha3 beta2 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-alpha3 beta2 /alpha3 beta4-containing nAChRs are functionally coupled to alpha (1 beta)- containing calcium channels. In contrast, Cd2+ blocks only 65% of nicotine- evoked norepinephrine release from hippocampal synaptosomes, indicating tha t a substantial fraction of this release occurs through mechanisms not invo lving calcium channels. This Cd2+-insensitive component of release is block ed by alpha -AuIB and therefore appears to be triggered by Ca2+ flowing dir ectly through the channels of presynaptic alpha3 beta4 nAChRs. Thus, these data indicate that different presynaptic termini can have distinctive funct ional associations of specific nAChRs and voltage-gated calcium channels.