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

Inserra MC, Israel MR, Caldwell A, Castro J, Deuis JR, Harrington AM, Keramidas A, Garcia-Caraballo S, Maddern J, Erickson A, Grundy L, Rychkov GY, Zimmermann K, Lewis RJ, Brierley SM, Vetter I (2017)


Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 7

Article Number: 42810

DOI: 10.1038/srep42810

Abstract

Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (Na V), 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 Na V 1.1-1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective Na V toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all Na V subtypes, an increase in the inactivation time constant was observed only at Na V 1.8, while the slope factor of the conductance-voltage curves was significantly increased for Na V 1.7 and peak current was significantly increased for Na V 1.6. Accordingly, P-CTX-1-induced visceral and cutaneous pain behaviours were significantly decreased after pharmacological inhibition of Na V 1.8 and the tetrodotoxin-sensitive isoforms Na V 1.7 and Na V 1.6, 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 Na V isoforms in peripheral sensory neurons and their contribution to membrane depolarisation, action potential initiation and propagation.

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APA:

Inserra, M.C., Israel, M.R., Caldwell, A., Castro, J., Deuis, J.R., Harrington, A.M.,... Vetter, I. (2017). Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1. Scientific Reports, 7. https://doi.org/10.1038/srep42810

MLA:

Inserra, Marco C., et al. "Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1." Scientific Reports 7 (2017).

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