Neurotoxins that Act on Voltage-Sensitive Sodium Channels in Excitable Membranes

A large number of biological toxins exert their toxic effects by modifying the properties of voltage-sensitive sodium channels involved in action po­ tential generation in nerve, heart, and skeletal muscle. These include the water-soluble heterocyclic guanidines, tetrodotoxin and saxitoxin, the lipid­ soluble polycyclic compounds, veratridine, aconitine, batrachotoxin, and grayanotoxin, and the low-molecular weight, basic polypeptide toxins iso­ lated from scorpion venoms and sea anemone nematocysts. The isolation, chemical characterization, and structure determination of many of these toxins as well as their systematic and comparative pharmacology have been the subject of previous excellent reviews. These aspects are, therefore, not treated in detail here. This review focuses on experiments that have given insight into the cellular and molecular mechanisms of action of these toxins and have revealed common features of their interaction with voltage-sensi­ tive sodium channels.