This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pyrethroids are widely used insecticides, especially in urban environments, to protect agricultural commodities and control vectors of human diseases. It is well established that pyrethroids modulate voltage-sensitive sodium channels;however, recent evidence suggests that voltage-sensitive calcium and chloride channels are also inhibited. Furthermore, pyrethroids modulate voltage-sensitive calcium channels at concentrations that elicit the in vivo acute neurotoxic symptoms of intoxication. The goal of this study is to determine relative indices of toxicity for pyrethroids on various human voltage-sensitive calcium channels expressed in vitro and validate the in vivo actions of pyrethroids. Xenopus oocytes, injected with human voltage-sensitive calcium channels cRNA, will be used to determine the direct and comparative action of pyrethroids on these channels.
The specific aims of the present proposal are 1) to examine the structure activity relationship of pyrethroids on the characteristics of human voltage-sensitive calcium channels. 2) to determine pyrethroid relative indices of toxicity on human voltage-sensitive calcium channels.
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