Neuron
Volume 9, Issue 1, July 1992, Pages 69-77
Journal home page for Neuron

Article
A new conus peptide ligand for mammalian presynaptic Ca2+ channels

https://doi.org/10.1016/0896-6273(92)90221-XGet rights and content

Abstract

Voltage-sensitive Ca2+ channels that control neurotransmitter release are blocked by w-conotoxin (ω-CgTx) GVIA from the marine snail Conus geographus, the most widely used inhibitor of neurotransmitter release. However, many mammalian synapses are ω-CgTx-GVIA insensitive. We describe a new Conus peptide, w-CgTxMVIIC, that is an effective inhibitor of ω-CgTx-GVIA-resistant synaptic transmission. Ca 2+ channel targets that are inhibited by ω-CgTx-MVIIC but not by ω-CgTx-GVIA include those mediating depolarization-induced 45Ca2+ uptake in rat synaptosome preparations, “P” currents in cerebellar Purkinje cells, and a subset of ω-CgTx-GVIA-resistant currents in CA1 hippocampal pyramidal cells. The characterization of ω-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.

References (24)

  • R. Llinas et al.

    Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison

  • E.W. McCleskey et al.

    Calcium channel blockade by a peptide from Conus: specificity and mechanism

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