Mechanisms of conotoxin inhibition of N-type (Cav2.2) calcium channels

Adams, David J. and Berecki, Géza (2013) Mechanisms of conotoxin inhibition of N-type (Cav2.2) calcium channels. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1828 7: 1619-1628. doi:10.1016/j.bbamem.2013.01.019

Author Adams, David J.
Berecki, Géza
Title Mechanisms of conotoxin inhibition of N-type (Cav2.2) calcium channels
Formatted title
Mechanisms of conotoxin inhibition of N-type (Cav2.2) calcium channels
Journal name Biochimica et Biophysica Acta (BBA) - Biomembranes   Check publisher's open access policy
ISSN 0005-2736
Publication date 2013-07
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.bbamem.2013.01.019
Open Access Status
Volume 1828
Issue 7
Start page 1619
End page 1628
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Formatted abstract
N-type (Cav2.2) voltage-gated calcium channels (VGCC) transduce electrical activity into other cellular functions, regulate calcium homeostasis and play a major role in processing pain information. Although the distribution and function of these channels vary widely among different classes of neurons, they are predominantly expressed in nerve terminals, where they control neurotransmitter release. To date, genetic and pharmacological studies have identified that high-threshold, N-type VGCCs are important for pain sensation in disease models. This suggests that N-type VGCC inhibitors or modulators could be developed into useful drugs to treat neuropathic pain. This review discusses the role of N-type (Cav2.2) VGCCs in nociception and pain transmission through primary sensory dorsal root ganglion (DRG) neurons (nociceptors). It also outlines the potent and selective inhibition of N-type VGCCs by conotoxins, small disulfide-rich peptides isolated from the venom of marine cone snails. Of these conotoxins, ω-conotoxins are selective N-type VGCC antagonists that preferentially block nociception in inflammatory pain models, and allodynia and/or hyperalgesia in neuropathic pain models. Another conotoxin family, α-conotoxins, were initially proposed as competitive antagonists of muscle and neuronal nicotinic acetylcholine receptors (nAChR). Surprisingly, however, α-conotoxins Vc1.1 and RgIA, also potently inhibit N-type VGCC currents in the sensory DRG neurons of rodents and α9 nAChR knockout mice, via intracellular signaling mediated by G protein-coupled GABAB receptors. Understanding how conotoxins inhibit VGCCs is critical for developing these peptides into analgesics and may result in better pain management. This article is part of a Special Issue entitled: Calcium channels.
Keyword Nociceptor
Neuropathic pain
N-type calcium channel
GABAB receptor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 24 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 27 Oct 2014, 18:02:10 EST by Sylvie Pichelin on behalf of Queensland Brain Institute