Abstract
Voltage-sensitive Ca2+ channels that control neurotransmitter release are blocked by omega-conotoxin (omega-CgTx) GVIA from the marine snail Conus geographus, the most widely used inhibitor of neurotransmitter release. However, many mammalian synapses are omega-CgTx-GVIA insensitive. We describe a new Conus peptide, omega-CgTx-MVIIC, that is an effective inhibitor of omega-CgTx-GVIA-resistant synaptic transmission. Ca2+ channel targets that are inhibited by omega-CgTx-MVIIC but not by omega-CgTx-GVIA include those mediating depolarization-induced 45Ca2+ uptake in rat synaptosome preparations, "P" currents in cerebellar Purkinje cells, and a subset of omega-CgTx-GVIA-resistant currents in CA1 hippocampal pyramidal cells. The characterization of omega-CgTx-MVIIC by a combination of molecular genetics and chemical synthesis defines a general approach for obtaining ligands with novel receptor subtype specificity from Conus.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Calcium Channel Blockers / pharmacology
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Calcium Channels / drug effects*
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Calcium Channels / metabolism
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Calcium Channels / physiology
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Cells, Cultured
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DNA / analysis
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DNA / genetics
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / ultrastructure
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Ligands
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Molecular Sequence Data
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Neurons / cytology
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Neurons / drug effects
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Neurons / ultrastructure
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Neurotransmitter Agents / antagonists & inhibitors
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Neurotransmitter Agents / metabolism
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Peptides / genetics
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Peptides / metabolism
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Peptides / pharmacology*
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Peptides, Cyclic / pharmacology
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Purkinje Cells / cytology
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Purkinje Cells / drug effects
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Purkinje Cells / ultrastructure
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Rats
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Snails
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Synapses / drug effects
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Synapses / metabolism
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Synapses / ultrastructure*
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omega-Conotoxin GVIA
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omega-Conotoxins*
Substances
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Calcium Channel Blockers
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Calcium Channels
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Ligands
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Neurotransmitter Agents
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Peptides
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Peptides, Cyclic
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omega-Conotoxins
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omega-conotoxin-MVIIC
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DNA
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omega-Conotoxin GVIA