Interaction of tetramethrin and deltamethrin at the single sodium channel in rat hippocampal neurons

Type I and type II pyrethroids are known to modulate the sodium channel to cause persistent openings during depolarization and upon repolarization. Although there are some similarities between the two types of pyrethroids in their actions on sodium channels, the pattern of modification of sodium currents is different between the two types of pyrethroids. In the present study, interactions of the type I pyrethroid tetramethrin and the type II pyrethroid deltamethrin at rat hippocampal neuron sodium channels were investigated using the inside-out single-channel patch clamp technique. Deltamertrin-modified sodium channels opened much longer than tetramethrin-modified sodium channels. When 10 muM tetramethrin was applied to membrane patches that had been exposed to 10 muM deltamethrin, deltamertrin-modified prolonged single sodium currents disappeared and were replaced by shorter openings which were characteristic of tetramethrin-modified channel openings. These single-channel data are compatible with previous whole-cell competition study between type I and type II pyrethroids. These results are interpreted as being due to the displacement of the type II pyrethroid molecule by the type I pyrethroid molecule from the same binding site or to the allosteric interaction of the two pyrethroid molecules as separate sodium channel sites. (C) 2001 Elsevier Science Inc. All rights reserved.