TRPV1 modulation of spinal cord synaptic transmission

TRPV1 调节脊髓突触传递

• 批准号: 7114557
• 负责人: GREGG W CRABTREE
• 金额: $ 3.58万
• 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: 2006-05-04 至 2008-05-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114557
• 关键词: action potentials; body temperature; calcium flux; calcium indicator; capsaicin; electrophysiology; heat; laboratory mouse; membrane activity; membrane channels; mixed tissue /cell culture; neural transmission; nociceptors; phospholipase C; predoctoral investigator; receptor coupling; receptor expression; spinal cord; spinal ganglion; temperature; tissue /cell preparation

DESCRIPTION (provided by applicant): This proposal examines the possible role of TRPV1, the capsaicin-noxious heat receptive ion channel, in modulating synaptic transmission between peripheral sensory neurons and dorsal horn spinal cord neurons. Although TRPV1 is normally not active at core body temperature, recent data in the literature have shown that either PLC activation or membrane depolarization can cause TRPV1 activation far below its nominal temperature threshold of activation of 43 degrees C. Electrophysiological studies performed at 37 degrees C in synaptic preparations will determine whether presynaptically-localized TRPV1 under conditions of either PLC activation or depolarization can modulate synaptic transmission in the spinal cord at physiological temperatures. As TRPV1 expressing sensory neurons are critical to the detection and processing of painful stimuli, the results of this project should have broad implications not only for the processing of normal painful stimuli but also towards understanding pathological pain states. Additionally, as TRPV1 has been reported to be expressed in both pyramidal neurons of the hippocampus and dopaminergic neurons of the substantia nigra, it is likely that the results of this study may have broad implications for synaptic physiology.

描述（由申请人提供）：本提案研究了 TRPV1（辣椒素毒性热接收离子通道）在调节外周感觉神经元和背角脊髓神经元之间的突触传递中的可能作用。尽管 TRPV1 通常在核心体温下不活跃，但文献中的最新数据表明，PLC 激活或膜去极化都可能导致 TRPV1 激活远低于其标称激活温度阈值 43 摄氏度。在 37 摄氏度下进行的电生理学研究突触准备工作将确定在 PLC 激活或去极化条件下突触前定位的 TRPV1 是否可以在生理温度下调节脊髓中的突触传递。由于表达 TRPV1 的感觉神经元对于疼痛刺激的检测和处理至关重要，因此该项目的结果不仅对正常疼痛刺激的处理而且对理解病理疼痛状态都具有广泛的影响。此外，据报道 TRPV1 在海马锥体神经元和黑质多巴胺能神经元中表达，因此这项研究的结果可能对突触生理学具有广泛的影响。