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Mar. Drugs 2017, 15(7), 232; doi:10.3390/md15070232

Ladder-Shaped Ion Channel Ligands: Current State of Knowledge

Group of Embryophysiology, N.K. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26, Vavilov st, 119334 Moscow, Russia
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Received: 16 June 2017 / Revised: 7 July 2017 / Accepted: 14 July 2017 / Published: 20 July 2017
(This article belongs to the Special Issue Marine Drugs and Ion Currents)
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Abstract

Ciguatoxins (CTX) and brevetoxins (BTX) are polycyclic ethereal compounds biosynthesized by the worldwide distributed planktonic and epibenthic dinoflagellates of Gambierdiscus and Karenia genera, correspondingly. Ciguatera, evoked by CTXs, is a type of ichthyosarcotoxism, which involves a variety of gastrointestinal and neurological symptoms, while BTXs cause so-called neurotoxic shellfish poisoning. Both types of toxins are reviewed together because of similar mechanisms of their action. These are the only molecules known to activate voltage-sensitive Na+-channels in mammals through a specific interaction with site 5 of its α-subunit and may compete for it, which results in an increase in neuronal excitability, neurotransmitter release and impairment of synaptic vesicle recycling. Most marine ciguatoxins potentiate Nav channels, but a considerable number of them, such as gambierol and maitotoxin, have been shown to affect another ion channel. Although the extrinsic function of these toxins is probably associated with the function of a feeding deterrent, it was suggested that their intrinsic function is coupled with the regulation of photosynthesis via light-harvesting complex II and thioredoxin. Antagonistic effects of BTXs and brevenal may provide evidence of their participation as positive and negative regulators of this mechanism. View Full-Text
Keywords: ciguatoxin; maitotoxin; brevetoxin; brevenol; voltage-gated Na+-channel; thylakoid membrane; light-harvesting complex II ciguatoxin; maitotoxin; brevetoxin; brevenol; voltage-gated Na+-channel; thylakoid membrane; light-harvesting complex II
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Shmukler, Y.B.; Nikishin, D.A. Ladder-Shaped Ion Channel Ligands: Current State of Knowledge. Mar. Drugs 2017, 15, 232.

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