Conotoxin modulation of voltage-gated sodium channels
Author(s)
Ekberg, J
Craik, DJ
Adams, DJ
Griffith University Author(s)
Year published
2008
Metadata
Show full item recordAbstract
The rising phase of the action potential in excitable cells is mediated by voltage-gated sodium channels (VGSCs), of which there are nine mammalian subtypes with distinct tissue distribution and biophysical properties. The involvement of certain VGSC subtypes in disease states such as pain and epilepsy highlights the need for agents that modulate VGSCs in a subtype-specific manner. Conotoxins from marine snails of the Conus genus constitute a promising source of such modulators, since these peptide toxins have evolved to become selective for various membrane receptors, ion channels and transporters in excitable cells. This ...
View more >The rising phase of the action potential in excitable cells is mediated by voltage-gated sodium channels (VGSCs), of which there are nine mammalian subtypes with distinct tissue distribution and biophysical properties. The involvement of certain VGSC subtypes in disease states such as pain and epilepsy highlights the need for agents that modulate VGSCs in a subtype-specific manner. Conotoxins from marine snails of the Conus genus constitute a promising source of such modulators, since these peptide toxins have evolved to become selective for various membrane receptors, ion channels and transporters in excitable cells. This review covers the structure and function of three classes of conopeptides that modulate VGSCs: the pore-blocking 季onotoxins, the d-conotoxins which delay or inhibit VGSC inactivation, and the 叭conotoxins which inhibit VGSC Na+ conductance independent of the tetrodotoxin binding site. Some of these toxins have potential therapeutic and research applications, in particular the 叭conotoxins, which may develop into potential drug leads for the treatment of pain states.
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View more >The rising phase of the action potential in excitable cells is mediated by voltage-gated sodium channels (VGSCs), of which there are nine mammalian subtypes with distinct tissue distribution and biophysical properties. The involvement of certain VGSC subtypes in disease states such as pain and epilepsy highlights the need for agents that modulate VGSCs in a subtype-specific manner. Conotoxins from marine snails of the Conus genus constitute a promising source of such modulators, since these peptide toxins have evolved to become selective for various membrane receptors, ion channels and transporters in excitable cells. This review covers the structure and function of three classes of conopeptides that modulate VGSCs: the pore-blocking 季onotoxins, the d-conotoxins which delay or inhibit VGSC inactivation, and the 叭conotoxins which inhibit VGSC Na+ conductance independent of the tetrodotoxin binding site. Some of these toxins have potential therapeutic and research applications, in particular the 叭conotoxins, which may develop into potential drug leads for the treatment of pain states.
View less >
Journal Title
The International Journal of Biochemistry and Cell Biology
Volume
40
Issue
11
Publisher URI
Subject
Biochemistry and cell biology
Medical biochemistry and metabolomics
Cellular nervous system
Medical physiology