NOCICEPTORS AND GLUTAMATE RECEPTORS

伤害感受器和谷氨酸受体

• 批准号: 6540312
• 负责人: AMY B MACDERMOTT
• 金额: $ 21.31万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540312
• 关键词: AMPA receptors; action potentials; afferent nerve; axon; calcium indicator; capsaicin; cell population study; dendrites; dorsal horn; electrophysiology; flow cytometry; glutamate receptor; heat stimulus; imaging /visualization /scanning; immunocytochemistry; kainate; laboratory rat; mixed tissue /cell culture; neurons; nociceptors; receptor expression; spinal ganglion; stainings

DESCRIPTION (adapted from applicant's abstract): Cutaneous nociceptors are a heterogeneous group of peripheral sensory neurons that sense noxious, damage-causing stimuli in the periphery and transmit that signal to the central nervous system. They extend their processes peripherally and centrally from cell bodies located in the dorsal root ganglia (DRG). The primary site of termination of the central projection of these unmyelinated and lightly myelinated fibers is predominantly in the superficial laminae (I and II) of the spinal cord dorsal horn. There are multiple subpopulations of nociceptors with cells bodies in the dorsal root ganglion (DRG). They can be grouped by sensory modality, by intracellular markers such as peptides, or by surface markers such as those developed and characterized by Dodd and Jessell (1985). We will use immunocytochemistry to identify DRG nociceptor subpopulations. We will test individual populations of nociceptors for expression of several nociceptive properties including low and high threshold heat and capsaicin sensitivity, using Ca2+ imaging and electrophysiology to measure responses. Kainate and AMPA receptors are expressed on subpopulations of DRG neurons, including functionally identified nociceptors, although the subpopulations of nociceptors have not yet been identified. Kainate and AMPA receptors expressed by nociceptors have been suggested to contribute to detection of damaging stimuli in the skin (Carlton and Coggeshall, 1995; Jackson and Hargreaves, 1995). There is immunocytochemical evidence for peripheral kainate and AMPA receptor expression (Coggeshall and Carlton, 1998) that could underlie such a transduction mechanism. There is physiological evidence that DRG neurites central to the ganglion itself respond to kainate, suggesting kainate or AMPA receptors may have a function at the central terminals of nociceptors, as well (Agrawal and Evans, 1986). Using the spinal cord slice preparation with attached dorsal root and co-cultures of identified nociceptors and dorsal horn neurons, we will investigate where AMPA and kainate receptors are expressed central to the DRG and specifically whether they are expressed on the nociceptor nerve terminals. We will determine the impact of receptor activation on glutamate release from the primary afferent terminals.

描述（改编自申请人的摘要）：皮肤伤害感受器是一种 感觉有害， 并将信号传送到中枢 神经系统它们的进程从外围和中心延伸， 位于背根神经节（DRG）的细胞体。的原发部位 终止这些无髓鞘和轻度的中央投射 有髓纤维主要位于脊髓的浅层（I和II）。 脊髓背角存在多种伤害感受器亚群， 背根神经节（DRG）的细胞体。它们可以按感觉分类 通过细胞内标记物如肽，或通过表面标记物如 如Dodd和Quarcell（1985）所发展和表征的那些。我们将使用 免疫细胞化学以鉴定DRG伤害感受器亚群。我们将测试 用于表达几种伤害感受器的个体群体 特性包括低和高阈值热和辣椒素敏感性， 使用Ca 2+成像和电生理学来测量反应。 红藻氨酸和 AMPA受体在DRG神经元的亚群上表达，包括 功能鉴定的伤害感受器，虽然伤害感受器的亚群 目前尚未查明。红藻氨酸和AMPA受体表达的 伤害感受器被认为有助于检测损害性刺激 （Carlton和科格斯霍尔，1995;杰克逊和哈格里夫斯，1995）。那里 是外周红藻氨酸和AMPA受体免疫细胞化学证据 表达式（科格斯霍尔和卡尔顿，1998年），可以根据这样一个 转导机制有生理学证据表明背根神经节神经突起 中枢神经节本身对红藻氨酸有反应，表明红藻氨酸或AMPA 感受器也可能在伤害感受器的中央末端起作用 （Agrawal和Evans，1986年）。使用脊髓切片制备， 附着的背根以及识别的伤害感受器和背角的共培养物 神经元，我们将研究AMPA和红藻氨酸受体表达的地方 DRG的核心，特别是它们是否表达在 伤害感受器神经末梢我们将确定受体激活的影响 对初级传入神经末梢释放谷氨酸的影响