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Title
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Neuronal calcium channel inhibitors. Synthesis of omega-conotoxin GVIA and effects on 45Ca uptake by synaptosomes.
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Authors
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J.Rivier,
R.Galyean,
W.R.Gray,
A.Azimi-Zonooz,
J.M.McIntosh,
L.J.Cruz,
B.M.Olivera.
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Ref.
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J Biol Chem, 1987,
262,
1194-1198.
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PubMed id
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Abstract
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We previously described a 27-amino acid peptide neurotoxin from the venom of
Conus geographus, omega-conotoxin GVIA, which inhibits neuronal
voltage-activated calcium channels. In this paper we describe the total
synthesis of omega-conotoxin GVIA and demonstrate that it efficiently blocks
voltage-activated uptake of 45Ca by standard synaptosomal preparations from
chick brain. Dihydropyridines do not block 45Ca uptake under these conditions.
Thus, the omega-conotoxin-sensitive, but dihydropyridine-insensitive uptake of
45Ca2+ by chick brain synaptosomes serves as a functional assay for a Ca channel
target of omega-conotoxin. The use of synthetic GVIA should rapidly accelerate
our understanding of the molecular biology of Ca2+ channels and their role in
neuronal function.
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