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

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Inserra, Marco C
Israel, Mark R
Caldwell, Ashlee
Castro, Joel
Deuis, Jennifer R
Harrington, Ann Chrystine
Keramidas, Angelo
Garcia-Caraballo, Sonia
Maddern, Jessica
Erickson, Andelain
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Nature Publishing Group
© The Author(s) 2017
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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.
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ciguatoxin, Human intoxication, fish-borne illness
Inserra, M. C., Israel, M. R., Caldwell, A., Castro, J., Deuis, J. R., Harrington, A. M., ... & Grundy, L. (2017). Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1. Scientific Reports, 7.