Role of mechanically activated ion channels in somatosensation

项目概要/摘要 支配皮肤和肌肉的体感神经元在感知中发挥着重要作用 触觉、疼痛和本体感觉。相同类型的感觉神经元支配其他器官 经历频繁的机械刺激。此类器官/组织的清单包括骨骼、 牙齿、肺、脉管系统、胃和膀胱。从解剖学上讲，颅神经节（包括 三叉神经节）支配头部，而结状/颈静脉和背根神经节（DRG）支配头部 身体的其余部分。机械激活 (MA) 非选择性阳离子通道的作用 Piezo2 在 DRG 中用于感应触摸和本体感觉的技术已经很成熟。然而，少得多的是 了解 Piezo2（以及一般的机械转导）在其他感觉神经节中的作用 支配颅面区域和其他内脏器官。例如，重复和 我们的呼吸系统承受着广泛的机械力。肺的拉伸是 由结状/颈静脉、三叉神经和胸背根神经节中的神经元及其细胞体感知。 机械驱动的反射被认为对于正常的肺功能至关重要。然而， 机械力转导的精确生理意义和分子机制 肺部仍然模糊。在本提案中提供的初步数据中，我们表明 Piezo2 是 在支配气道的神经元中表达。我们进一步表明，全局和感觉神经元特异性 Piezo2 的消融会导致呼吸窘迫症状。在初步的基础上 此处提供的数据，我们将研究 Piezo2 在呼吸和各种 颅面组织。

PROJECT SUMMARY/ABSTRACT Somatosensory neurons that innervate the skin and muscle play an essential role in sensing touch, pain, and proprioception. The same type of sensory neurons innervates other organs that experience frequent mechanical stimulation. This list of such organs/tissues includes bone, teeth, lung, vasculature, stomach, and bladder. Anatomically, cranial ganglia (including trigeminal) innervate the head, while nodose/jugular and dorsal root ganglia (DRG) innervate the rest of the body. The role of the mechanically activated (MA) non-selective cation channel Piezo2 in DRGs for sensing touch and proprioception is well established. However, much less is known about the role of Piezo2 (and mechanotransduction in general) in other sensory ganglia that innervate the craniofacial region and other internal organs. For example, repetitive and wide-ranging mechanical forces are experienced by our respiratory system. Lung stretch is sensed by neurons with their cell bodies in the nodose/jugular, trigeminal, and thoracic DRGs. Mechanically-driven reflexes are thought to be crucial for proper lung function; however, the precise physiological significance and molecular mechanism of mechanotransduction within the lung remains obscure. In preliminary data presented in this proposal, we show that Piezo2 is expressed in neurons innervating the airways. We further show that global and sensory neuronspecific ablation of Piezo2 causes symptoms of respiratory distress. Building on the preliminary data presented here, we will investigate the role of Piezo2 in respiration and in various craniofacial tissues.