Nerve membrane ionic channels as the target of toxicants.

Certain natural toxins and environmental agents have been found to act on nerve membrane ionic channels in a highly specific manner. For example, the puffer fish poison, tetrodotoxin, blocks the sodium channel without affecting its gating mechanism. The sodium channel is also the major target site of the pyrethroid and DDT insecticides. Patch clamp single channel recording experiments with cultured neuroblastoma cells have revealed that individual sodium channels are kept open much longer in the presence of the pyrethroid tetramethrin than in control. This effect accounts for a marked prolongation of sodium current by tetramethrin observed in giant axons. The prolonged sodium current increases the depolarizing after-potential which in turn generates repetitive after-discharges. The symptoms of pyrethroid poisoning in animals can be explained on this basis. Only a very small fraction of sodium channels, less than 1%, needs to be modified by pyrethroids to produce the symptoms of poisoning. Fenvalerate, a cyano-containing type II pyrethroid, prolongs the sodium channel open time much more drastically than tetramethrin. This causes a persistent depolarization of the membrane, which in turn blocks conduction.