CORE--ELECTROPHYSIOLOGY AND ANATOMY

核心——电生理学和解剖学

• 批准号: 6564578
• 负责人: DOJU YOSHIKAMI
• 金额: $ 14.53万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564578
• 关键词: Xenopus; Xenopus oocyte; animal poison; autoradiography; biomedical facility; calcium channel blockers; chemical binding; conotoxin; electrical measurement; electrophysiology; goldfish; histology; laboratory mouse; laboratory rat; membrane channels; neuroanatomy; neuromuscular transmission; neuropeptides; neurotoxins; voltage /patch clamp; voltage gated channel

The electrophysiology section of this core will screen conotoxins for their functional activities against known ion channel targets as well as identify possible new targets for novel conotoxins. The anatomy section of the Core will identify the sites of conotoxin binding in mammalian brain by autoradiography following exposure to 125I-labeled conotoxins. These anatomical experiments assessing the binding of toxins to their targets will complement the physiological experiments assessing the toxins' effects on target function. 1. OBJECTIVES 1. Qualitative screening of conotoxins for their effects on known ion channel targets, both voltage-and ligand-gated. 2. Quantitative determination of the potencies of toxins (and derivatives) in affecting their targets' function. A given toxin's ability to affect a given class of ion channels can differ depending on the specific tissue, cell type, or species of animal wherein the channel resides, so comparative pharmacology can be involved. When appropriate, kinetic, in addition to equilibrium, constants will be determined. 3. Identification of the locations of the binding sites of the conotoxins within the mammalian CNS, and characterization of the affinity of these sites for toxin. 4. Identification and characterization of new targets for novel toxins.

该核心的电生理学部分将筛选芋螺毒素 它们针对已知离子通道目标的功能活动以及 确定新型芋螺毒素的可能新目标。解剖部分 核心将识别芋螺毒素在哺乳动物大脑中的结合位点 通过暴露于 125I 标记的芋螺毒素后进行放射自显影。这些 评估毒素与其目标结合的解剖实验 将补充评估毒素的生理实验 对目标功能的影响。 1. 目标 1. 芋螺毒素对已知离子影响的定性筛选 通道目标，电压门控和配体门控。 2. 毒素效力的定量测定（和 衍生物）影响其目标的功能。特定毒素的能力 影响给定类别的离子通道可能会有所不同，具体取决于 动物的特定组织、细胞类型或物种，其中通道 存在，因此可以涉及比较药理学。在适当的时候， 除了平衡之外，还将确定动力学常数。 3. 结合位点位置的鉴定 哺乳动物中枢神经系统内的芋螺毒素及其亲和力的表征 这些位点的毒素。 4. 新型靶点的识别和表征 毒素。