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

DSC1 阳离子通道家族在昆虫神经生理学和神经毒素中的作用

基本信息

批准号：
8242084
负责人：
KE DONG
金额：
$ 28.05万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8242084
关键词：
Aedes Afferent Neurons Alternative Splicing Ankle Anopheles gambiae Basic Science Behavior Biological Assay Cations Chemicals Chest Culicidae Development Dictyoptera Drosophila genus Drosophila melanogaster Family Family Study Fiber Future Gene Family Generations Genes Genetic Goals Grant Insect Repellents Insect Vectors Insecta Insecticides Invertebrates Ion Channel Knock-out Knowledge Leg Malaria Mammals Methods Molecular Motor Motor Neurons Muscle Nerve Nerve Endings Nervous system structure Organ Pathway interactions Pheromone Play Positioning Attribute Property RNA Editing RNA Interference RNA Splicing Research Role Sensory Shapes Signal Transduction Site Smell Perception Sodium Channel System Testing Toxicology Transcript Variant base decamethrin fighting human disease in vivo inhibitor/antagonist interest knockout gene member mutant neural circuit neurophysiology neurotoxicology novel pyrethroid receptor research study response tibia voltage

项目摘要

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.

使用杀虫剂和驱避剂控制病媒昆虫是防治一些最致命的人类疾病，比如疟疾。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成分，如电压门控的钠通道和嗅觉系统。20年前，一个类似钠通道的基因， DSC 1（Drosophila sodium channel 1，果蝇钠通道1）是从黑腹果蝇中克隆出来的。尽管近20年来，人们一直认为DSC 1编码一种电压门控钠离子通道，基于其与钠通道的序列相似性，我们最近发现DSC 1 和它在蟑螂中的直向同源物BSC 1，编码一个新家族的创始成员，电压门控阳离子通道。我们最近的基因敲除实验表明，在调节D.对避蚊胺（一种驱虫剂）的敏感性，溴氰菊酯（一种拟除虫菊酯类杀虫剂），暗示DSC 1家族阳离子通道重要昆虫神经生理学和毒理学方面的专家。本项目的长期目标是全面了解 DSC 1家族的阳离子通道在调节昆虫神经回路和对杀虫剂、引诱剂和驱避剂。一个整合的分子，电生理，药理学和遗传学方法将被用来实现这一目标。的具体目标建议的资助期限是：1）分子和电生理表征的DSC 1 阳离子通道家族; 2）确定阳离子通道的DSC 1家族在昆虫化学感觉和神经毒理学; 3）了解DSC 1通道的作用调节特定的神经回路这项基础研究应该加强我们的基础了解新发现的离子通道家族在昆虫神经生理学中的作用和毒理学研究结果可为未来开发新一代的杀虫剂或提高目前使用的杀虫剂，引诱剂，或驱虫剂。