Role of mechanically activated ion channels in somatosensation

描述(由申请人提供)：涉及机械力感应的离子通道的身份仍然难以捉摸。机械激活(MA)阳离子通道起着触摸/疼痛传感器的作用，也是听力、调节血管张力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发现了MA阳离子通道组分，命名为Piezo1和Piezo2。在多种哺乳动物细胞系中表达Piezos可引起较大的MA阳离子电流。此外，我们发现在体感神经元中针对Piezo2的RNAi可以特异性地下调快速适应的MA阳离子电流。在这里，我们测试了Piezo2是体感机械转导所必需的假设 公共卫生相关性：TSRI机械感觉与关节炎和颞下颌关节紊乱等疾病引起的炎症性疼痛状态密不可分，在这些疾病中，即使是最微小的关节运动(行走、咀嚼和说话)也会导致疼痛，并导致慢性头痛和耳鸣等症状。因此，对热感觉和机械感觉的分子理解对疼痛领域是重要的和相关的。

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.