Abstract
Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their analogs, are naturally occurring alkaloids with divergent evolutionary origins and biogeographical distribution, but which share the common chemical feature of guanidinium moieties. These guanidinium groups confer high biological activity with high affinity and ion flux blockage capacity for voltage-gated sodium channels (NaV). Members of the STX group, known collectively as paralytic shellfish toxins (PSTs), are produced among three genera of marine dinoflagellates and about a dozen genera of primarily freshwater or brackish water cyanobacteria. In contrast, toxins of the TTX group occur mainly in macrozoa, particularly among puffer fish, several species of marine invertebrates and a few terrestrial amphibians. In the case of TTX and analogs, most evidence suggests that symbiotic bacteria are the origin of the toxins, although endogenous biosynthesis independent from bacteria has not been excluded. The evolutionary origin of the biosynthetic genes for STX and analogs in dinoflagellates and cyanobacteria remains elusive. These highly potent molecules have been the subject of intensive research since the latter half of the past century; first to study the mode of action of their toxigenicity, and later as tools to characterize the role and structure of NaV channels, and finally as therapeutics. Their pharmacological activities have provided encouragement for their use as therapeutants for ion channel-related pathologies, such as pain control. The functional role in aquatic and terrestrial ecosystems for both groups of toxins is unproven, although plausible mechanisms of ion channel regulation and chemical defense are often invoked. Molecular approaches and the development of improved detection methods will yield deeper understanding of their physiological and ecological roles. This knowledge will facilitate their further biotechnological exploitation and point the way towards development of pharmaceuticals and therapeutic applications.
Highlights
Many living forms have developed complex neurological systems to receive and transduce vital information from the environment where they live and to elicit appropriate behavioral responses to such stimuli
Voltage-gated ion channels are the target for a wide range of naturally occurring toxins, including guanidinium and secondary amine analogs and various polypeptide and protein neurotoxins
Toxin analogs belonging to the STX and TTX families share common guanidinium moieties (Figure 1), which accounts for their neurotoxicity and similar molecular targets, but these toxin groups differ widely in organismal origin and biogeography
Summary
Many living forms have developed complex neurological systems to receive and transduce vital information from the environment where they live and to elicit appropriate behavioral responses to such stimuli. Generation of neuro-electrical signals is crucial for sensory functions including transmission and processing of information in the neurological center (or brain), and for muscle contraction, secretion of hormones and distributing response signals to the rest of the tissues All these electrical signals are conducted by members of the ion channel protein superfamily, comprising more than 140 structurally related pore-forming proteins [1]. The guanidinium neurotoxins, namely saxitoxin (STX), tetrodotoxin (TTX), and their numerous analogs, are naturally occurring alkaloids with a high affinity for binding to NaV channels, blocking the influx of Na+ ions into the cell. This blockage inhibits the propagation of action potentials in excitable membranes, and this impediment causes effective neuro-muscular paralysis. Within the last 50 years, such dinoflagellate blooms known to produce to STX analogs have apparently expanded in biogeographical range, and have contributed to increased magnitude and frequency of toxic events around the world
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
