Ladder-Shaped Ion Channel Ligands: Current State of Knowledge

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.

Characterization of maitotoxin‐4 (MTX4) using electrospray positive mode ionization high‐resolution mass spectrometry and UV spectroscopy

“…Recent studies revealed that G. excentricus is one of the most toxic species known to date for production of both ciguatoxins (CTXs) and maitotoxins (MTXs) 3–7 . CTXs are the main known causative agents of CP 8 . Although they have very low oral potency, 7,9 MTXs are very toxic following intraperitoneal injection 10 and feeding studies by Kohli et al 11 in laboratory‐controlled conditions have shown they may accumulate in fish muscle.…”

Development of New Synthetic Methods Using Oxiranyl Anions and Application in the Syntheses of Polycyclic Ether Marine Natural Products

“…A limitation of this approach is the inability of ring expansion for ketone 52, presumably due to severe steric congestion of the 1,3-diaxial methyl groups. 40) These results demonstrate the synthetic utility of the oxiranyl anion strategy combined with the ring expansion reaction in the synthesis of polycyclic ether natural products. 42) causes the same characteristic rounding of cultured mouse neuroblastoma cells as brevetoxins A and B and shows cytotoxicity at a concentration of 5 µmol.…”

Isolation and Characterization of aRhizobiumBacterium Associated with the Toxic DinoflagellateGambierdiscus balechii

“…The density of Gambierdiscus spp. in natural waters usually fluctuates widely within a short period; however, analyses of environmental factors such as temperature, salinity, or nutrients have not attributed these fluctuations to any of these factors [37]. It is possible that interactions with bacteria affect the population variation of Gambierdiscus spp.…”