Role of the DSC1 family of cation channels in insect neurophysiology and neurotox

使用杀虫剂和驱虫剂控制病媒是防治虫害的重要战略。 一些最具破坏性的人类疾病，如疟疾。许多杀虫剂和昆虫 今天使用的驱虫剂针对昆虫神经系统的组件，如电压门控 钠通道和嗅觉系统。二十年前，一种类似钠通道的基因， 命名为DSC1(果蝇钠通道1)，是从果蝇中克隆的。 尽管近二十年来，DSC1一直被认为编码一种电压门控钠 基于其与钠通道的序列相似性，我们最近发现DSC1 和它在蟑螂中的同源基因BSC1，编码了一个新的家族的创始成员 电压门控阳离子通道。我们最近的基因敲除实验表明，DSC1 在调节黑腹果蝇对驱虫剂DEET(一种驱虫剂)和 溴氰菊酯(一种拟除虫菊酯杀虫剂)，涉及重要的DSC1家族阳离子通道 昆虫神经生理学和毒理学的玩家。 这个项目的长期目标是全面了解这一角色 DSC1家族阳离子通道在调节昆虫神经回路中的作用及对 杀虫剂、引诱剂和驱虫剂。一种集成了分子、电生理、 将采取药理学和遗传学的方法来实现这一目标。《公约》的具体目标 建议的授权期是：1)DSC1的分子和电生理特性 阳离子通道家族；2)DSC1家族阳离子通道在 昆虫的化学感觉和神经毒理学；以及3)了解DSC1通道的作用 调制特定的神经回路。这项基础研究应该加强我们的基础 一个新发现的离子通道家族在昆虫神经生理学中的作用 和毒物学。研究结果可为新一代网络的未来发展提供基础 杀虫剂或新方法，以提高目前使用的杀虫剂、引诱剂、 或者驱虫剂。

Use of insecticides and repellents to control insect vectors is an important strategy for fighting some of the most devestating human diseases, such as malaria. Many insecticides and insect repellents used today target components of the insect nervous system, such as voltage-gated sodium channels and the olfaction system. Two decades ago, a sodium channel-like gene, called DSC1 (Drosophila sodium channel 1), was cloned from Drosophila melanogaster. Although for nearly two decades DSC1 had been thought to encode a voltage-gated sodium channel based on its sequence similarity to sodium channels, we recently showed that DSC1 and its orthologue in cockroach, BSC1, encode the founding members of a novel family of voltage-gated cation channels. Our recent gene knockout experiments suggest that DSC1 plays a crucial role in modulating D. melanogaster sensitivity to DEET (an insect repellent) and deltamethrin (a pyrethroid insectcide), implicating DSC1-family cation channels as important players in insect neurophysiology and toxicology. The long-term goal of this project is to reach a comprehensive understanding of the role of the DSC1 family of cation channels in modulating insect neuroral circuitry and sensitivity to insectcides, attractants, and repellents. An integrated molecular, electrophysiological, pharmacological, and genetic approach will be taken to achieve this goal. Specific aims of the proposed grant period are: 1) molecular and electrophysiological characterization of the DSC1 family of cation channels; 2) determination of the role of the DSC1 family of cation channels in insect chemosensation and neurotoxicology; and 3) understanding the role of the DSC1 channel in modulating specific neural circuits. This basic research should enhance our fundamental knowledge of the role of a newly discovered family of ion channels in insect neurophysiology and toxicology. Results could provide a basis for future development of a new generation of insecticides or new methods to enhance the efficacy of currently used insecticides, attractants, or repellents.