Transmitter release from peripheral sensory neurons

周围感觉神经元释放递质

• 批准号: 7760190
• 负责人: AMY B MACDERMOTT
• 金额: $ 34.5万
• 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/7760190
• 关键词: Action Potentials; Afferent Neurons; Body Temperature; C Fiber; Caliber; Cations; Cells; Coculture Techniques; Detection; Electrophysiology (science); Fiber; Glutamates; Heating; Image; Investigation; Kinetics; Lead; 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.

专门用于检测伤害性刺激、温度和瘙痒的外周感觉神经具有它们的功能。 皮肤、肌肉、骨骼和内脏中的外周终末，其胞体位于背根神经节中 (DRG)其中枢终末位于脊髓背角。刺激由AD和C纤维携带， 小直径的感觉神经元，其中许多表达有害的热敏受体TRPV 1， Ca 2+渗透性阳离子通道。TRPV 1在DRG神经元的外周感觉末梢中作为一种神经递质， 多种伤害性刺激的主要传感器，包括43 ℃以上的伤害性热刺激。尽管如此- TRPV 1在背角DRG神经元的中枢突触末梢上的存在， 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， TRPV 1在核心体温（~ 37 ℃）下， TRPVI的正常激活温度阈值为43 ℃。第一个条件是 温度和电压之间的关系。在静息膜电位下，TRPV 1显示可测量的，紧张的 在37 ℃下活化。随后的去极化导致TRPV 1激活的显著增加（Voets et 等人，2004）。然而，大多数关于TRPV 1在中枢终末功能的研究都是在 室温，而不是体温。其次，PLC偶联受体的激活导致 TRPVI的激活温度阈值的显著降低导致其即使在室温下也能激活 温度（Chuang et al，2001）。我们建议测试的假设，在生理或身体 温度下，以及在受体介导的PLC活化或生理条件下， 和离子型受体递质介导的膜去极化 中枢感觉末梢的激活是实质性的，并且这种激活将导致突触的调节。 在DRG-脊髓突触的传递。这些研究集中在疼痛通路的关键部分; 外周感觉纤维与中枢神经系统的交叉点，它们将提供对 新的调节机制。