Saxitoxins sodium channel blocking

Saxitoxin and its derivatives are water-soluble compounds that bind to the voltage-sensitive sodium channel, blocking propagation of nerve-muscle action potentials. The natural route of exposure to these toxins is oral. In a BW scenario, the most likely route of delivery is by inhalation or toxic projectile. In addition, saxitoxin could be used in a confined area to contaminate water supplies. 

Action potentiai propagation Local anesthetics, tetrodo-toxin, saxitoxin Nerve axons Block sodium channels block conduetbn... 

Saxitoxin, the best known example of this group, is a potent neurotoxin found in shellfish such as mussels, clams, and scallops. Saxitoxin is a sodium channel-blocking agent and is more toxic by inhalation than by other routes of exposure. Unlike oral intoxication with saxitoxin (paralytic shellfish poisoning), which has a relatively slow onset, inhala-tional intoxication with saxitoxin can be lethal in a few minutes. Saxitoxin could be used against our troops as an antipersonnel weapon, but because it cannot currently be chemically synthesized efficiently, or produced easily in large quantities from natural sources, it is unlikely to be seen as an area aerosol weapon on the battlefield. 

Like saxitoxin, zetekitoxin AB is a selective sodium channel blocker however, its sodium channel blocking activity was 580-fold higher than that of saxitoxin [169]. Sadly, the Panamanian golden frog is now extinct. 

TTX) and saxitoxin, which block the channel pore from the outer side. The difference in TTX sensitivity among the sodium channels is caused by a single amino acid difference in the P region of repeat I (phenylalanine or tyrosine in TTX-sensitive channels cysteine or serine in TTX-resistant channels). The S6 segments contribute to forming the inner pore of the channel and binding sites for local anesthetics. 

Figure 11. Comparative potencies of several saxitoxins and tetrodotoxin in the mouse bioassay, displacement of radiolabelled saxitoxin from rabbit brain, and block of single batrachotoxin-treated rat sarcolemmal sodium channels incorporated into planar lipid bilayers. The horizontal axis is the log of the potency relative to saxitoxin. Compound numbering corresponds to that in Figure 1. Data from Ref. 10, 94, 95.

The tetrodotoxins (TTXs) and saxitoxins (STXs) have in common the ability to block sodium channels of excitable membranes (1—5), Saxitoxin and tetrodotoxin are some of the most potent non-proteinaceous neurotoxins known and are responsible for significant human morbidity and mortality (6, 7). Although for many years the biosynthetic origin(s) of TTXs and STXs has not been identified, recent evidence indicates that bacteria may be a source. 

Terlau, H., Heinemann, S. H., Stiihmer, W. et al. Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II. FEBS Lett. 293,93-96,1991. 

This structure for saxitoxin (15) was presented at the first Conference on Poisonous Dinoflagellates at Boston, Mass, in November 1974 and published in the Journal of the American Chemical Society, March, 1975 (16). On the basis of this structure, Tanino et al. (17) with Kishi at Harvard University synthesized d,l-saxi-toxin and it was found active in blocking sodium channels in the same manner as natural saxitoxin. Later Bordner et al. (18) working with Rapoport confirmed our structure for saxitoxin with an X-ray analysis of saxitoxin ethyl hemiketal. 

Saxitoxin (32) is listed in Schedule 1 of the CWC. It is a polar, cationic, relatively low molecular mass toxin and is one of 18 structurally related neurotoxins collectively known as paralytic shellfish poisoning (PSP) toxins. Analogues are formed by addition of sulfate, A-sulfo and A-hydroxyl groups, and by decarbamylation. They block neuronal sodium channels, and thereby neurotransmission, death resulting from respiratory paralysis. Saxitoxin is produced by dinoflagellate species (and by some freshwater cyanobacteria), and accumulates in shellfish. The cationic nature of saxitoxin makes capillary electrophoresis combined with... 

AH these toxins act in the same way nervous transmission is blocked when the PSP binds to site 1 of the sodium channels (CatteraU, 1980), and this induces muscle paralysis. In animals, typical neurological effects induced by this toxin include nervousness, jumping, jerking, ataxia, convulsions, and paralysis. The paralysis of respiratory muscles is fatal within a few minutes (Runnegar et al., 1988). Saxitoxins are toxic both by ingestion and by inhalation, and they could be dispersed as aerosols and inhaled, and so lead to rapid respiratory collapse and death. 

Different ion channels maintain the stability of excitable membranes that are necessary for normal functioning of the body. Saxitoxin, tetrodotoxin, and DDT all cause toxicity by blocking the sodium channel in excitable membranes. On the other hand, organic solvents cause toxicity by changing the membrane fluidity of the neurones in the central nervous system. 

Saxitoxin binds to the sodium channels in the membranes of excitable cells (neurons and muscle cells) blocking synaptic transmission. Saxitoxin is connected to red tides. Saxitoxin reduces nerve conduction velocities. 

Neosaxitoxin, saxitoxin, and gongantoxin I-IV block transmission of impulses between nerve and muscle. They also block sodium channels in nerve and skeletal muscle, inhibiting the nerve and muscle action potential, thereby blocking nerve conduction and muscle contraction. 

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