We have studied the voltage-activated influx of Ca2+ into synaptosomes. Rapid 45Ca2+ influx into synaptosomes, measured at 1 sec, was blocked by predepolarization and by low concedntrations of cadmium (IC50, 1 μM), as anticipated for voltage-sensitive calcium channels (VSCCs). However, fluxes were insensitive to dihydropyridine drugs that block or activate VSCCs, including nitrendipine, Bay K 8644, and (+)- and (-)-PN202-791. Phenylalkylamine calcium antagonists, including verapamil and desmethoxyverapamil, blocked 45Ca2+ uptake in a nonspecific fashion. The peptide ω-conotoxin fraction GVIA (ω-CgTx GVIA) blocked 45Ca2+ uptake in a biphasic fashion, with a 30% reduction at 50 pM toxin and a further decrease at concentrations > 5 nM. The toxin inhibited neurotransmitter release from synaptosomes in nanomolar concentrations, corresponding to its low-affinity effects on 45Ca2+ influx. ω-CgTx GVIA also inhibited depolarization-induced increases in intracellular Ca2+ concentration in single hippocampal and striatal neurons. These findings indicate that ω-CgTx GVIA blocks VSCCs in both cell bodies and nerve terminals and that the predominant form of VSCC in nerve terminals is the dihydropyridine-insensitive N type.
|Original language||English (US)|
|Number of pages||4|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1986|
ASJC Scopus subject areas