Brain voltage-sensitive calcium channel subtypes differentiated by ω-conotoxin fraction GVIA

I. J. Reynolds, J. A. Wagner, S. H. Snyder, S. A. Thayer, B. M. Olivera, R. J. Miller

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Abstract

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 languageEnglish (US)
Pages (from-to)8804-8807
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number22
DOIs
StatePublished - Dec 1 1986

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