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: 7790605
• 负责人: KE DONG
• 金额: $ 28.34万
• 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/7790605
• 关键词: Aedes; Afferent Neurons; 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; neuronal circuitry; neurophysiology; neurotoxicology; novel; public health relevance; 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(申请人提供)：使用杀虫剂和驱虫剂来控制昆虫媒介是抗击一些最具破坏性的人类疾病的重要战略，例如疟疾。今天使用的许多杀虫剂和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。20年前，从果蝇中克隆了一种类似钠通道的基因，称为DSC1(果蝇钠通道1)。虽然近20年来，DSC1被认为编码电压门控钠通道，因为它与钠通道序列相似，但我们最近发现，DSC1及其在蟑螂中的同源基因BSC1编码了一个新的电压门控阳离子通道家族的创始成员。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和拟除虫菊酯杀虫剂溴氰菊酯的敏感性方面起着至关重要的作用，这意味着DSC1家族阳离子通道在昆虫神经生理学和毒理学中发挥着重要作用。该项目的长期目标是全面了解DSC1家族阳离子通道在调节昆虫神经回路和对杀虫剂、引诱剂和驱虫剂的敏感性中的作用。为了实现这一目标，将采取分子、电生理、药理学和遗传学的综合方法。建议的授权期的具体目标是：1)DSC1阳离子通道家族的分子和电生理特征；2)确定DSC1阳离子通道家族在昆虫化学感觉和神经毒理学中的作用；以及3)了解DSC1通道在调节特定神经回路中的作用。这项基础研究将加强我们对一个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础知识。这一结果可能为未来开发新一代杀虫剂或提高目前使用的杀虫剂、引诱剂或驱虫剂的效力的新方法提供基础。公共卫生相关性迫切需要制定新的战略，有效控制包括疟疾在内的人类疾病的昆虫媒介。这项建议旨在了解一类新的昆虫离子通道在神经生理学和神经毒理学中的作用。这项研究有可能为未来开发新一代杀虫剂或提高目前使用的杀虫剂、引诱剂或驱虫剂的效力的新方法提供基础。