title: Voltage-sensitive Ca2+ channels involved in nicotinic receptor-mediated [3H]dopamine release from rat striatal synaptosomes.
abstract: The potent nicotinic agonist anatoxin-a elicits mecamylamine-sensitive [3H]dopamine release from striatal synaptosomes, and this action is both Na+ and Ca2+ dependent and is blocked by Cd2+. This suggests that stimulation of presynaptic nicotinic receptors results in Na+ influx and local depolarisation that activates voltage-sensitive Ca2+ channels, which in turn provide the Ca2+ for exocytosis. Here we have investigated the subtypes of Ca2+ channels implicated in this mechanism. [3H]-Dopamine release evoked by anatoxin-a (1 microM) was partially blocked by 20 microM nifedipine, whereas KCl-evoked release was insensitive to the dihydropyridine. However, a 86Rb+ efflux assay of nicotinic receptor function suggested that nifedipine has a direct effect on the receptor, discrediting the involvement of L-type channels. The N-type Ca2+ channel blocker omega-conotoxin GVIA (1 microM) blocked anatoxin-a-evoked [3H]dopamine release by 60% but had no significant effect on 86Rb+ efflux; release evoked by both 15 and 25 mM KCl was inhibited by only 30%. The P-type channel blocker omega-agatoxin IVA (90 nM) also inhibited KCl-evoked release by approximately 30%, whereas anatoxin-a-evoked release was insensitive. The Q-type channel blocker omega-conotoxin MVIIC (1 microM) had no effect on either stimulus. These results suggest that presynaptic nicotinic receptors on striatal nerve terminals promote [3H]dopamine release by activation of N-type Ca2+ channels. In contrast, KCl-evoked [3H]dopamine release appears to involve both N-type and P-type channels.
authors.affiliation: School of Biology and Biochemistry, University of Bath, Bath, England, UK.
authors.forename: L
authors.initials: L
authors.lastname: Soliakov
authors.forename: S
authors.initials: S
authors.lastname: Wonnacott
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D000087522:Cyanobacteria Toxins; D004298:Dopamine / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology; D052998:Microcystins; D017072:Neostriatum / Q000737:chemistry* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism; D014326:Tropanes
chemical_list: D001427:Bacterial Toxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D009498:Neurotoxins; D011978:Receptors, Nicotinic; D014326:Tropanes; D002104:Cadmium; D014316:Tritium; D011189:Potassium Chloride; C509783:anatoxin a; D009543:Nifedipine; D002118:Calcium; D004298:Dopamine