Role of mechanically activated ion channels in somatosensation

描述（由申请人提供）：参与传感机械力的离子通道的身份仍然难以捉摸。机械激活 (MA) 阳离子通道充当触摸/疼痛传感器，​​并且也是听力、血管张力调节和其他功能所必需的。事实上，机械转导是分子水平上最不为人所知的感觉转导系统。我们最近在脊椎动物中鉴定出 MA 阳离子通道成分，名为 Piezo1 和 Piezo2。在多种哺乳动物细胞系中表达 Piezos 会诱导大的 MA 阳离子电流。此外，我们发现体感神经元中针对 Piezo2 的 RNAi 特异性下调快速适应的 MA 阳离子电流。在这里，我们测试了体感机械转导需要 Piezo2 的假设 公共健康相关性：TSRI 机械感觉与关节炎和颞下颌关节紊乱等疾病引起的炎性疼痛状态有着千丝万缕的联系，即使是最轻微的关节运动（行走、咀嚼和说话）也会引起疼痛，并导致慢性头痛和耳鸣等症状。因此，对热和机械感觉的分子理解非常重要并且与疼痛领域相关。

DESCRIPTION (provided by applicant): The identity of ion channels involved in sensing mechanical force has remained elusive. Mechanically-activated (MA) cation channels function as touch/pain sensors, and are also required for hearing, adjustment of vascular tone and other functions. Indeed, mechanotransduction is the least understood sensory transduction system at the molecular level. We recently identified MA cation channel components in vertebrates named Piezo1 and Piezo2. Expressing Piezos in a variety of mammalian cell lines induce large MA cationic currents. Furthermore, we show that RNAi against Piezo2 in somatosensory neurons specifically downregulates rapidly-adapting MA cation currents. Here, we test the hypothesis that Piezo2 is required for somatosensory mechanotransduction PUBLIC HEALTH RELEVANCE: TSRI Mechanical sensation is inextricably linked to inflammatory pain states caused by diseases such as Arthritis and Temperomandibular Disorders, where even minimal movement of joints (walking, chewing, and speaking) cause pain and lead to symptoms such as chronic headache and ringing in the ears. Therefore, a molecular understanding of thermal and mechanical sensation is important and relevant to the field of pain.