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

• 批准号: 8047944
• 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
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8047944
• 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; Health; 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; neuronal circuitry; neurophysiology; neurotoxicology; novel; pyrethroid; receptor; research study; response; tibia; voltage

DESCRIPTION (provided by applicant): Use of insecticides and repellents to control insect vectors is an important strategy for fighting some of the most devastating 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 insecticide), 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 neuronal circuitry and sensitivity to insecticides, 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. PUBLIC HEALTH RELEVANCE Development of new strategies for effective control of insect vectors of human diseases, including malaria, is urgently needed. This proposal is aimed at understanding the role of a new family of insect ion channels in neurophysiology and neurotoxicology. This research has the potential to 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.

描述（由申请人提供）：使用杀虫剂和驱虫剂来控制昆虫媒介是与疟疾等最毁灭性人类疾病作斗争的重要策略。如今，许多杀虫剂和驱虫剂都使用昆虫神经系统的成分，例如电压门控钠通道和嗅觉系统。二十年前，从果蝇Melanogaster克隆了一种称为DSC1（果蝇1频道1）的钠频道样基因。尽管近二十年来，DSC1被认为根据其与钠通道的序列相似性编码了电压门控通道，但最近我们表明，DSC1及其在蟑螂中的直系同源物BSC1编码了一个新型伏特 - 伏特 - 伏特的创始成员。门控阳离子通道。我们最近的基因敲除实验表明，DSC1在调节D. melanogaster对DEET的敏感性（一种驱虫剂）和三甲虫（一种杀虫剂杀虫剂）方面起着至关重要的作用，这意味着DSC1-家庭阳离子阳离子通道是昆虫神经生理学和毒理学中的重要参与者。该项目的长期目标是对DSC1阳离子通道家族在调节昆虫神经元电路中的作用以及对杀虫剂，吸引剂和驱虫剂的敏感性的作用。将采用综合分子，电生理，药理和遗传方法来实现这一目标。拟议的授予期的具体目的是：1）DSC1阳离子通道家族的分子和电生理表征； 2）确定阳离子通道DSC1家族在昆虫化学化和神经毒理学中的作用； 3）了解DSC1通道在调节特定神经回路中的作用。这项基础研究应增强我们对新发现的离子通道家族在昆虫神经生理学和毒理学中的作用的基本知识。结果可以为将来开发新一代杀虫剂或新方法提供基础，以增强当前使用的杀虫剂，吸引剂或驱虫剂的功效。迫切需要开发公共卫生相关性的新策略，以有效控制包括疟疾在内的人类疾病的昆虫媒介。该建议旨在理解新的昆虫离子通道家族在神经生理学和神经毒理学中的作用。这项研究有可能为将来开发新一代杀虫剂或新方法提供基础，以增强当前使用的杀虫剂，吸引剂或驱虫剂的功效。