INTERACTIONS OF TETRAMETHRIN, FENVALERATE AND DDT AT THE SODIUM-CHANNEL IN RAT DORSAL-ROOT GANGLION NEURONS

Type I and type II pyrethroids and dichlorodiphenyltrichloroethane (DD T) are known to modulate the sodium channel to cause the hyperexcitato ry symptoms of poisoning in animals. However, since the degrees to whi ch neuronal sodium channel parameters are altered differ, a question i s raised as to whether these insecticides bind to the same site in the sodium channel. Competition patch-clamp experiments were performed us ing rat dorsal root ganglion neurons which are endowed with tetrodotox in-sensitive and tetrodotoxin-resistant sodium channels. D-trans-Tetra methrin, S,S-fenvalerate and p,p'-DDT caused a slowly rising and slowl y falling tail current to be developed in tetrodotoxin-sensitive sodiu m channels. In tetrodotoxin-resistant sodium channels, these insectici des, particularly tetramethrin and fenvalerate, generated a large and prolonged tail current upon repolarization. The effects of tetramethri n were reversible after washing with drug-free solution, whereas the e ffects of fenvalerate and DDT were irreversible. When fenvalerate appl ication was followed by tetramethrin application, the characteristic c hanges in current by fenvalerate disappeared and the characteristic ch anges by tetramethrin appeared. After washout, the characteristic curr ent pattern of fenvalerate reappeared. These results can be explained by assuming that the tetramethrin molecule displaces the fenvalerate m olecule from the same binding site in the sodium channel protein, or t hat tetramethrin and fenvalerate bind to separate sodium channel sites which interact allosterically with each other. DDT interacted with fe nvalerate and tetramethrin in the same manner.