Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1

Inserra, Marco C., Isreal, Mathilde, Caldwell, Ashlee, Castro, Joel, Deuis, Jennifer R., Harrington, Andrea M., Keramidas, Angelo, Garcia-Caraballo, Sonia, Maddern, Jessica, Erickson, Andelain, Grundy, Luke, Rychkov, Grigori Y., Zimmerman, Katharina, Lewis, Richard J., Brierley, Stuart M. and Vetter, Irina (2017) Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1. Scientific Reports, 7 . doi:10.1038/srep42810

Author Inserra, Marco C.
Isreal, Mathilde
Caldwell, Ashlee
Castro, Joel
Deuis, Jennifer R.
Harrington, Andrea M.
Keramidas, Angelo
Garcia-Caraballo, Sonia
Maddern, Jessica
Erickson, Andelain
Grundy, Luke
Rychkov, Grigori Y.
Zimmerman, Katharina
Lewis, Richard J.
Brierley, Stuart M.
Vetter, Irina
Title Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2017-02-22
Year available 2017
Sub-type Article (original research)
DOI 10.1038/srep42810
Open Access Status DOI
Volume 7
Total pages 19
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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Created: Mon, 06 Mar 2017, 10:38:41 EST by Angelo Keramidas on behalf of Queensland Brain Institute