Cu2+ induces Ca2+-dependent neurotransmitter release from brain catecholaminergic nerve terminals.
CuCl2, ZnCl2 and NiCl2, but not CdCl2 or CoCl2, induced transmitter release from superfused rat hippocampal and striatal synaptosomes preloaded with, respectively, [3H]noradrenaline and [3H]dopamine. Cu2+ was the most potent and effective, acting in a concentration- (0.1-300 microM) and time-dependent (peak effect occurring at 2-3 min) manner. The amount of Cu2+-induced release over a 5 min period is similar to that induced by depolarization with high KCl or the K+ channel blocker 4-aminopyridine. However, the time course of the Cu2+-induced release is slower and the effect of Cu2+ is not reversed by washout. Cu2+-induced catecholamine release requires extracellular calcium (Ca2+) and is inhibited by the Ca2+ channel blocker Cd2+, and in the case of noradrenaline, by the voltage-gated Na+ channel blocker tetrodotoxin. The ability of Cu2+ to induce massive Ca2+-dependent transmitter release from brain catecholaminergic nerve terminals may contribute to the neuropathological processes associated with Cu2+ toxicity in Wilson's disease.
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA. jwang@opal.tufts.edu
J K
JK
Wang
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D019216:Metals, Heavy / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D002395:Catecholamines; D002413:Cations, Divalent; D019216:Metals, Heavy; D018377:Neurotransmitter Agents; D013779:Tetrodotoxin; D003300:Copper; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine