N-type calcium channels are involved in the dopamine releasing effect of nicotine.
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.
Harsing
L G
LG
Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962.
Sershen
H
H
Vizi
S E
SE
Lajtha
A
A
D000704:Analysis of Variance; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010456:Peptides, Cyclic; D002104:Cadmium; D009538:Nicotine; D020866:omega-Conotoxin GVIA; D004298:Dopamine