Transmitter release from peripheral sensory neurons

周围感觉神经元释放递质

• 批准号: 7363688
• 负责人: AMY B MACDERMOTT
• 金额: $ 34.75万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-03 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7363688
• 关键词: Action Potentials; Afferent Neurons; Body Temperature; C Fiber; Caliber; Cations; Cells; Chromosome Pairing; Coculture Techniques; Condition; Detection; Electrophysiology (science); Fiber; Glutamates; Heating; Image; Investigation; Kinetics; Lead; Localized; Measurable; Mediating; Membrane; Membrane Potentials; Muscle; Neuraxis; Neurons; Nociceptors; Pain; Pathway interactions; Peripheral; Phospholipase; Physiological; Preparation; Presynaptic Terminals; Receptor Activation; Research Personnel; Rest; Role; Sensory; Skin; Slice; Spinal; Spinal Cord; Spinal Ganglia; Stimulus; Synapses; Synaptic Transmission; System; TRP channel; TRPV1 gene; Temperature; Testing; Training; Transducers; Viscera; afferent nerve; bone; dorsal horn; gamma-Aminobutyric Acid; insight; neuronal cell body; presynaptic; programs; receptor; receptor coupling; sensor; transmission process; voltage

The peripheral sensory nerves specialized for detection of noxious stimuli, temperature and itch have their peripheral terminals in the skin, muscle, bone and viscera, their cell bodies in the dorsal root ganglion (DRG), and their central terminals in the spinal dorsal horn. The stimuli are carried by AD and C-fibers of small diameter sensory neurons, many of which express the noxious heat-sensitive receptor, TRPV1, a Ca2+ permeable cation channel. TRPV1 in the peripheral sensory terminals of DRG neurons serves as a major transducer of multiple noxious stimuli, including noxious thermal stimuli above 43oC. Despite the well- established presence of TRPV1 on the central synaptic terminals of DRG neurons in the dorsal horn, its physiological relevance there has not been clearly established. Recent findings imply that under certain conditions, TRPV1 can be expected to become active at core body temperature (~37oC), well below TRPVI's normal 43oC temperature threshold for activation. The first condition involves the interaction between temperature and voltage. At resting membrane potentials, TRPV1 shows measurable, tonic activation at 37oC. Subsequent depolarization leads to substantial increases in TRPV1 activation (Voets et al, 2004). However, most investigations of TRPV1 function in central terminals have been carried out at room temperature rather than body temperature. Second, activation of PLC-coupled receptors leads to a dramatic reduction in TRPVI's temperature threshold of activation leading to its activation even at room temperature (Chuang et al, 2001). We propose to test the hypothesis that at physiological or body temperatures, and under the conditions of either receptor mediated PLC activation or physiological membrane depolarization mediated by action potentials and ionotropic receptor transmitters, TRPV1 activation in central sensory terminals is substantial and that this activation will lead to modulation of synaptic transmission at DRG-spinal cord synapses. These studies focus on a critical part of the pain pathway; the intersection of the peripheral sensory fiber with the central nervous systems and they will provide insight into new regulatory mechanisms in that pathway.

专门检测有害刺激、温度和瘙痒的外周感觉神经有其自身的功能。 皮肤、肌肉、骨骼和内脏的末梢，其细胞体位于背根神经节 （DRG），以及它们在脊髓背角的中央末端。刺激由 AD 纤维和 C 纤维携带 小直径感觉神经元，其中许多表达有害热敏受体 TRPV1， Ca2+ 可渗透的阳离子通道。 DRG 神经元外周感觉末梢中的 TRPV1 充当 多种有害刺激的主要传感器，包括 43oC 以上的有害热刺激。尽管情况良好—— 确定TRPV1存在于背角DRG神经元的中央突触末端，其 其生理相关性尚未明确确定。最近的研究结果表明，在某些情况下 条件下，TRPV1 预计会在核心体温 (~37oC) 下变得活跃，远低于 TRPVI 的正常激活温度阈值为 43oC。第一个条件涉及交互 温度和电压之间。在静息膜电位下，TRPV1 显示出可测量的强直性 37℃激活。随后的去极化导致 TRPV1 激活显着增加（Voets 等） 等人，2004）。然而，大多数关于TRPV1在中央终端功能的研究都是在 室温而不是体温。其次，PLC耦合受体的激活导致 TRPVI 的激活温度阈值大幅降低，即使在室温下也能激活 温度（Chuang 等人，2001）。我们建议检验以下假设：在生理或身体上 温度，并在受体介导的 PLC 激活或生理条件下 由动作电位和离子型受体递质 TRPV1 介导的膜去极化 中枢感觉末梢的激活是显着的，并且这种激活将导致突触的调节 DRG-脊髓突触的传输。这些研究重点关注疼痛通路的关键部分；这 周围感觉纤维与中枢神经系统的交叉点，它们将提供对 该途径中的新监管机制。