Analgesic alpha-conotoxins Vc1.1 and RgIA inhibit N-type calcium channels in sensory neurons of alpha9 nicotinic receptor knockout mice

Callaghan, Brid and Adams, David J. (2010) Analgesic alpha-conotoxins Vc1.1 and RgIA inhibit N-type calcium channels in sensory neurons of alpha9 nicotinic receptor knockout mice. Channels, 4 1: 51-54. doi:10.4161/chan.4.1.10281


Author Callaghan, Brid
Adams, David J.
Title Analgesic alpha-conotoxins Vc1.1 and RgIA inhibit N-type calcium channels in sensory neurons of alpha9 nicotinic receptor knockout mice
Formatted title
Analgesic α-conotoxins Vc1.1 and Rg1A inhibit N-type calcium channels in sensory neurons of α9 nicotinic receptor knockout mice
Journal name Channels   Check publisher's open access policy
ISSN 1933-6969
1933-6950
Publication date 2010-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.4161/chan.4.1.10281
Volume 4
Issue 1
Start page 51
End page 54
Total pages 4
Place of publication Austin, TX, United States
Publisher Landes Bioscience
Collection year 2011
Language eng
Subject 920111 Nervous System and Disorders
1109 Neurosciences
C1
Formatted abstract
α-Conotoxins Vc1.1 and Rg1A are peptides from the venom of marine Conus snails that are currently in development as a treatment for neuropathic pain. We have reported previously that the α9α10 nicotinic acetylcholine receptor (nAChR) selective-conotoxins Vc1.1 and Rg1A potently and selectively inhibit high voltage-activated (HVA) N-type calcium channel currents in dissociated neurons from rat dorsal root ganglia (DRG). Our data indicated that Vc1.1 does not interact directly with N-type Ca2+ channels but inhibits them via GABAB receptor activation. The present study investigated Vc1.1 and Rg1A inhibition of N-type Ca2+ channels currents in DRG neurons of wild-type and α9 knockout (KO) mice to determine if the α9 nAChR was necessary for inhibition of the Ca2+ channel current. Application of Vc1.1 (100 nM) inhibited N-type Ca2+ channel currents to 69.2 ± 3.5% of control in DRG neurons isolated from wild-type mice. In {greater than or equal to >70% of DRG neurons isolated from the α9 KO mice, both Vc1.1 and Rg1A selectively inhibited N-type Ca2+ channel currents with an IC50 of 24.6 nM and 22.4 nM, respectively. The GABAB receptor antagonist CGP55845 (1 μM) antagonized the effect of Vc1.1 and Rg1A on the N-type Ca2+ channels in α9 KO mice. RT-PCR and western blot analysis confirmed the absence of the α9 nAChR in mice carrying a null mutation for the nAChR α9 gene. These results demonstrate that the inhibition of N-type Ca2+ channel channels by Vc1.1 and Rg1A is not mediated by the expression of α9α10 nAChRs in DRG neurons.
© Landes Bioscience
Keyword Conotoxin
Nicotinic Receptors
Alpha 9 knockout mice
N-type calcium channel
Dorsal root ganglion
GABA(B) receptor
Analgesia
Acetylcholine-receptors
Hair-cells
Pain
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Queensland Brain Institute Publications
 
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Created: Sun, 09 May 2010, 10:04:55 EST