Conotoxin modulation of voltage-gated sodium channels

J. Ekberg, D. J. Craik, David J. Adams

Research output: Contribution to journalShort surveyResearchpeer-review

44 Citations (Scopus)

Abstract

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 μ-conotoxins, the δ-conotoxins which delay or inhibit VGSC inactivation, and the μO-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 μO-conotoxins, which may develop into potential drug leads for the treatment of pain states.

Original languageEnglish
Pages (from-to)2363-2368
Number of pages6
JournalInternational Journal of Biochemistry and Cell Biology
Volume40
Issue number11
DOIs
Publication statusPublished - 2008
Externally publishedYes

Fingerprint

Conotoxins
Voltage-Gated Sodium Channels
Modulation
Therapeutic Human Experimentation
Conus Snail
Pain
Tetrodotoxin
Tissue Distribution
Ion Channels
Modulators
Action Potentials
Epilepsy
Binding Sites
Tissue
Membranes
Peptides
Pharmaceutical Preparations

Cite this

Ekberg, J. ; Craik, D. J. ; Adams, David J. / Conotoxin modulation of voltage-gated sodium channels. In: International Journal of Biochemistry and Cell Biology. 2008 ; Vol. 40, No. 11. pp. 2363-2368.
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Conotoxin modulation of voltage-gated sodium channels. / Ekberg, J.; Craik, D. J.; Adams, David J.

In: International Journal of Biochemistry and Cell Biology, Vol. 40, No. 11, 2008, p. 2363-2368.

Research output: Contribution to journalShort surveyResearchpeer-review

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AU - Craik, D. J.

AU - Adams, David J.

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AB - 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 μ-conotoxins, the δ-conotoxins which delay or inhibit VGSC inactivation, and the μO-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 μO-conotoxins, which may develop into potential drug leads for the treatment of pain states.

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