Transmitter release from peripheral sensory neurons

周围感觉神经元释放递质

• 批准号: 7176036
• 负责人: AMY B MACDERMOTT
• 金额: $ 32.57万
• 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/7176036
• 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

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：专门检测有害刺激、温度和瘙痒的外周感觉神经，其外周末梢在皮肤、肌肉、骨骼和内脏，其细胞体在背根神经节（DRG），其中央末梢在脊髓背角。刺激由小直径感觉神经元的AD和c纤维携带，其中许多表达有害的热敏受体TRPV1，一种Ca2+渗透性阳离子通道。DRG神经元外周感觉末端的TRPV1是多种有害刺激的主要换能器，包括43℃以上的有害热刺激。尽管TRPV1存在于背角DRG神经元的中枢突触末端，但其生理相关性尚未明确确立。最近的研究结果表明，在某些条件下，TRPV1可以在核心体温（~37℃）下激活，远低于TRPVI正常的43℃激活阈值。第一个条件涉及温度和电压之间的相互作用。在静息膜电位下，TRPV1在37℃时表现出可测量的强直激活。随后的去极化导致TRPV1激活大幅增加（Voets et al, 2004）。然而，大多数关于TRPV1中枢末梢功能的研究都是在室温而不是体温下进行的。其次，plc偶联受体的激活导致TRPVI的激活温度阈值急剧降低，即使在室温下也能激活（Chuang et al, 2001）。我们提出在生理或体温下，在受体介导的PLC激活或由动作电位和嗜离子受体递质介导的生理膜去极化的条件下，TRPV1在中枢感觉终端的激活是实质性的，并且这种激活将导致drg -脊髓突触突触传递的调节。这些研究集中在疼痛通路的一个关键部分；外周感觉纤维与中枢神经系统的交叉点它们将为这条通路中的新调控机制提供洞见。