Tetrodotoxin binding site

With respect to toxins which target specific sites, insight can be obtained from the anomolies that are observed. For example, both puffer fish and tetrodotoxin-containing crabs (96) are insensitive to tetrodotoxin. The investigation of such insensitivities can provide information about membrane channels and their toxin binding sites. 

Lembi CA (2003) Control of nuisance algae. In Wehr JD, Sheath RG (eds) Freshwater algae of North America ecology and classification. Academic, San Diego, CA, pp 805-834 Lipkin GM, Fozzard HA (1994) A structural model of the tetrodotoxin and saxitoxin binding site of the Na+ channel. Biophys J 66 1-13... 

A variety of toxins that modulate voltage-gated sodium channels have been used to probe channel function. They can be classified on the basis of five discrete binding sites (Table 1). These binding sites are commonly found on all a-subunits and are being characterized at the molecular level. The sensitivity to the puffer fish poison tetrodotoxin (TTX) has been used to subdivide voltage-gated sodium channels (Table 3). 

The extreme toxic potential of marine metabolites often prevents their application in medicine. However, a number of metabolites proved to be valuable tools in biochemistry, cell and molecular biology. For instance the neurotoxic maitotoxin [109-112] (interaction with extracellular calcium enhancement of calcium influx [113]), the neurotoxic brevetoxin B [114] (interaction with the binding-site-5 of voltage-sensitive sodium channels [115]), tetrodotoxin and saxitoxin (voltage clamp analysis to study sodium channels and excitatory phenomena [116] tetrodotoxin abolishes brevetoxin B activity [117]), okadaic acid [118-120] (analysis of phosphorylation and dephosphorylation processes in eukaryotic cell metabolism [121]), and palytoxin (stimulation of arachidonic acid metabolism synergistically with TPA-type promoters [122]). 

The interaction of (+)-kavain with receptor site 1 of Na channels, which is the epitope of antagonists like saxitoxin and tetrodotoxin, and its influence on site 2, the binding site of agonists including veratridine, batrachotoxin, and aconitine, were investigated on cerebrocortical synaptosomes by radioligand-binding assays. 

Moczydlowski, E.M., Mahar, J., Ravindran, A., 1988. Multiple saxitoxin-binding sites in bullfrog muscle tetrodotoxin-sensitive sodium channels and tetrodotoxin-insensitive sites of unknown function". Mol. Pharmacology, 33 202-211. 

Binding site 1 I S2-S6, II S2-S6 III S2-S6, IV S2-S6 Tetrodotoxin Saxitoxin T-Conotoxin Pore plugging... 

Tetrodotoxin and saxitoxin, which block the voltage-dependent sodium channels, prevent and actually reverse batrachotoxin-elicited depolarizations. The blockade by tetrodotoxin occurs at a different channel site than that at which batrachotoxin acts. Classical anesthetics, however, would appear to antagonize the action of batrachotoxin through competition for the binding site (50 and references therein). Local anesthetics have been shown to block but perhaps not reverse the action of batrachotoxin in squid axon (79), rat diaphragm (77), eel electroplax (55), frog nerve 160, 765), synaptosomes (706, 179), and neuroblastoma cells (50, 755, 756). 

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