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Modulation of spike generation in somatosensory endings of the cornea - the role of chloride currents in inflammatory sensitization

角膜体感末端尖峰产生的调节——氯电流在炎症敏化中的作用

基本信息

批准号：
213632774
负责人：
Professor Dr. Stephan Frings
金额：
--
依托单位：
Forschungsgruppe Molekulare Physiologie der Tiere
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/213632774?language=en
关键词：
Modulation spike generation somatosensory endings

项目摘要

Afferent signals arising from sensory end organs are subject to considerable modulation even before reaching the spinal cord. Sensory neurons may adapt, they may be sensitized, or may even be overtly switched on or off. The molecular processes underlying such regulation have attracted considerable research effort but have only rarely been deciphered in detail. In the somatosensory system of mammals, the response characteristics of individual primary sensory neurons can be altered dramatically by the immune system. Inflammatory mediators sensitize nerve terminals and boost the intensity of stimulus-induced afferent signals. Based on recent concepts of peripheral inflammatory hyperalgesia, we examine the hypothesis that such sensitization is promoted by depolarizing chloride currents.To explore the effects of chloride currents in primary afferent neurones, we will analyse somatosensory fibres in the cornea of the mammalian eye. In two parallel and complementary approaches, we will study the expression of chloride transporters and chloride channels in corneal axons and, at the same time, examine chloride-related aspects of spike generation in corneal nerve terminals. The two approaches are designed to clarify two questions: (1) Which protein equipment mediates chloride effects in somatosensory nerve terminals; and (2) how are these proteins involved in the sensitization of nerve terminals during inflammation? To address these questions we combine studies of protein expression and protein regulation with the determination of nerve terminal sensitivity in the presence of inflammatory mediators. This project will add considerably to our understanding of plasticity in the somatosensory system through a novel approach to peripheral hyperalgesia.

从感觉末端器官产生的传入信号甚至在到达脊髓之前就受到相当大的调制。感觉神经元可能会适应，它们可能会变得敏感，甚至可能会被公开地打开或关闭。这种调节背后的分子过程吸引了大量的研究工作，但很少被详细破译。在哺乳动物的体感系统中，免疫系统可以显着改变单个初级感觉神经元的反应特征。炎症介质使神经末梢敏感并增强刺激引起的传入信号的强度。基于最近的周围炎症痛觉过敏的概念，我们检验了这种敏化是通过去极化氯电流促进的假设。为了探索氯电流对初级传入神经元的影响，我们将分析哺乳动物眼睛角膜中的体感纤维。在两种并行和互补的方法中，我们将研究角膜轴突中氯转运蛋白和氯通道的表达，同时检查角膜神经末梢中尖峰生成的氯相关方面。这两种方法旨在澄清两个问题：（1）哪种蛋白质设备介导体感神经末梢的氯效应；（2）这些蛋白质如何参与炎症过程中神经末梢的敏化？为了解决这些问题，我们将蛋白质表达和蛋白质调节的研究与炎症介质存在下神经末梢敏感性的测定结合起来。该项目将通过一种新的外周痛觉过敏方法，大大加深我们对体感系统可塑性的理解。