The objective of this research is to elucidate the mechanism of action of insecticides on the nerve membrane which is the most critical target site of a variety of insecticides. Advanced electrophysiological techniques developed in our laboratory for the study of insecticides will be fully utilized, including intracellular microelectrode, voltage clamp, intracellular perfusion, and gating current measurement. The insecticides used for this study are a variety of synthetic pyrethroids and DDT and its analogs and derivatives. The proposed study is divided into nine specific projects. 1) Kinetics of insecticide-sodium channel interactions will be analyzed using voltage clamp methods. 2) The actions of two types of pyrethroids, one being a stimulating type and the other depolarizing type, will be characterized. 3) The structure-activity relationship of pyrethroids will be established for the two types of action. 4) The mechanism by which isomers exert differential effects will be studied. 5) DDT and its analogs will be compared with pyrethroids to determine similarities and differences in action. 6) The effects of pyrethroids and DDT on gating current will be studied. 7) Ionic selectivity of the sodium cnannels modified by pyrethroids will be determined. 8) The effects of two types of pyrethroids on synapses and sensory cells will be studied to find out common features of the two types in exerting symptoms of poisoning. 9) The mechanism underlying the effects of temperature on pyrethroid and DDT action will be studied using voltage clamp methods. These studies are expected to provide the basis for the molecular mechanism of action of insecticides and clues to improvement of the existing insecticides.
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