Nociceptive Ion Channels: mechanisms of activation

伤害性离子通道：激活机制

• 批准号: 7595846
• 负责人: Ardem Patapoutian
• 金额: $ 41.86万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7595846
• 关键词: Acidosis; Afferent Neurons; Behavior; Behavioral; Biological; Biological Assay; Biological Models; Biology; Bradykinin; Brain; Burn injury; Caenorhabditis elegans; Capsaicin; Charge; Chemicals; Chinese Hamster Ovary Cell; Cinnamon - dietary; Complex; Data; Drosophila genus; Esthesia; Exhibits; Family; Family member; Fire - disasters; Garlic; Genes; Genetic Screening; Goals; Grant; Hearing; Heating; Human; Human Genome Project; Hyperalgesia; Inflammation; Inflammation Mediators; Inflammatory; Injury; Invertebrates; Ion Channel; Ions; Laboratories; Learning; Mammals; Maps; Mass Spectrum Analysis; Mechanics; Methods; Modality; Molecular; Molecular Genetics; Mus; Mutagenesis; Nervous system structure; Neurons; Nociception; Nociceptors; Oils; Organism; Orthologous Gene; Pain; Pathway interactions; Perception; Peripheral; Play; Process; Proteins; Publications; Publishing; Research Personnel; Role; Sensory; Sensory Receptors; Signal Pathway; Signal Transduction; Stimulus; Suction; System; TRPV1 gene; Temperature; Testing; Tissues; Touch sensation; Withdrawal; Work; allicin; base; cinnamic aldehyde; fly; in vivo; member; mustard oil; novel; pressure; protein function; receptor; response; sensor; tool

While we usually take sensations such as pain, warmth or cold for granted, the molecules involved in these processes orchestrate a complex biological response to the outside world and remain almost a complete mystery. The sense of touch consists of the perception of multiple discrete types of thermal, mechanical and chemical stimuli. A great deal remains unknown about the genes involved in sensing these stimuli. With the completion of the human genome project, we have powerful new methods to identify these elusive sensory molecules. Using such tools, we recently cloned a novel sensory receptor, TRPA1, which responds to both painful cold stimuli and compounds known elicit painful sensations in humans. TRPA1 is a member of the Transient Receptor Potential (TRP) ion channel family; six members of this family respond to various temperatures. TRPA1 is highly conserved among mammals, flies, and worm. In mice, TRPA1 is expressed in sensory neurons thought to respond to several painful modalities such as heat, cold and mechanical injury. Upon activation of TRPA1 in sensory neurons, positively charged ions enter the neuron, which then fires and sends a pain signal to the brain. We wish to understand more about the consequences of TRPA1 activation in pain biology and sensation. TRPA1 is multi-modal in its activation. What other painful stimuli activate TRPA1? Mechanistically, how can a single receptor respond to so many stimuli? Can we learn more about nociceptive signaling and TRP channel signaling pathways by studying the role of TRPA1 in C. elegans?

虽然我们通常会认为疼痛，温暖或冷之类的感觉是理所当然的，但涉及的分子 流程策划了对外界的复杂生物学反应，并且几乎是一个完整的 神秘。触摸感包括对多种离散类型的热，机械和 化学刺激。关于感知这些刺激的基因，仍然未知很多。 随着人类基因组项目的完成，我们有强大的新方法来识别这些难以捉摸的 感觉分子。使用这样的工具，我们最近克隆了一个新型的感觉受体TRPA1，该受体响应 对于疼痛的冷刺激和已知的化合物都引起了人类的痛苦感觉。 TRPA1是会员 瞬态受体电势（TRP）离子通道家族；这个家庭的六名成员对各种 温度。 TRPA1在哺乳动物，苍蝇和蠕虫中是高度保守的。在小鼠中，TRPA1表示 在感官神经元中，人们被认为会响应几种痛苦的方式，例如热，冷和机械 受伤。 在感官神经元中激活TRPA1后，带正电的离子进入神经元，然后发射，然后发射 向大脑发送疼痛信号。我们希望更多地了解TRPA1激活的后果 在疼痛生物学和感觉中。 TRPA1的激活是多模式的。其他痛苦的刺激激活了什么 trpa1？从机械上讲，单个受体如何应对如此多的刺激？我们可以进一步了解 通过研究TRPA1在C中的作用。 秀丽隐杆线？