Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/105011
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Type: Journal article
Title: Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1
Author: Inserra, M.
Israel, M.
Caldwell, A.
Castro, J.
Deuis, J.
Harrington, A.
Keramidas, A.
Garcia-Caraballo, S.
Maddern, J.
Erickson, A.
Grundy, L.
Rychkov, G.
Zimmermann, K.
Lewis, R.
Brierley, S.
Vetter, I.
Citation: Scientific Reports, 2017; 7(1):42810-1-42810-19
Publisher: Nature Publishing Group
Issue Date: 2017
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Marco C. Inserra, Mathilde R. Israel, Ashlee Caldwell, Joel Castro, Jennifer R. Deuis, Andrea M. Harrington, Angelo Keramidas, Sonia Garcia-Caraballo, Jessica Maddern, Andelain Erickson, Luke Grundy, Grigori Y. Rychkov, Katharina Zimmermann, Richard J. Lewis, Stuart M. Brierley and Irina Vetter
Abstract: Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (NaV), causes ciguatera, a disease characterised by gastrointestinal and neurological disturbances. We assessed the activity of the most potent congener, Pacific ciguatoxin-1 (P-CTX-1), on NaV1.1-1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective NaV toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all NaV subtypes, an increase in the inactivation time constant was observed only at NaV1.8, while the slope factor of the conductance-voltage curves was significantly increased for NaV1.7 and peak current was significantly increased for NaV1.6. Accordingly, P-CTX-1-induced visceral and cutaneous pain behaviours were significantly decreased after pharmacological inhibition of NaV1.8 and the tetrodotoxin-sensitive isoforms NaV1.7 and NaV1.6, respectively. The contribution of these isoforms to excitability of peripheral C- and A-fibre sensory neurons, confirmed using murine skin and visceral single-fibre recordings, reflects the expression pattern of NaV isoforms in peripheral sensory neurons and their contribution to membrane depolarisation, action potential initiation and propagation.
Keywords: Ganglia, Spinal; Cells, Cultured; Animals; Humans; Mice; Ciguatoxins; Protein Isoforms; Gene Expression Regulation; Action Potentials; HEK293 Cells; Voltage-Gated Sodium Channels
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
RMID: 0030065193
DOI: 10.1038/srep42810
Appears in Collections:Medicine publications

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