Piezo2 senses airway stretch and mediates lung inflation-induced apnoea.
Piezo2 senses airway stretch and mediates lung inflation-induced apnoea.
复制标题
压电2感应气道拉伸并介导肺通胀引起的呼吸暂停。
DOI：
10.1038/nature20793
复制
发表时间：
2017-01-12
期刊：
影响因子：
64.8
通讯作者：
Patapoutian A
中科院分区：
文献类型：
--
作者：
Nonomura K;Woo SH;Chang RB;Gillich A;Qiu Z;Francisco AG;Ranade SS;Liberles SD;Patapoutian A
呼吸功能障碍是导致婴儿围产期死亡以及成人睡眠呼吸暂停的一个众所周知的原因，但呼吸控制机制尚未完全明晰。由支配气道的感觉神经元转导的机械信号对呼吸起到调控作用；然而，这些信号的生理意义和分子机制仍不明确。在此，我们发现，在新生小鼠中，整体及感觉神经元特异性敲除机械激活离子通道Piezo2会导致呼吸窘迫和死亡。对成年小鼠中Piezo2阳性迷走感觉神经元进行光遗传学激活会引发呼吸暂停。此外，诱导敲除成年小鼠感觉神经元中的Piezo2，会使神经元对肺膨胀的反应减弱、赫林 - 布雷尔机械反射受损，并且在正常条件下潮气量增加。在结状神经节中缺乏Piezo2的小鼠中也出现了这些表型。我们的数据表明，Piezo2是一种气道牵张感受器，并且Piezo2在各种支配气道的感觉神经元中介导的机械转导，对于出生时建立有效呼吸以及维持成人正常呼吸至关重要。
Respiratory dysfunction is a notorious cause of perinatal mortality in infants and sleep apnoea in adults, but the mechanisms of respiratory control are not clearly understood. Mechanical signals transduced by airway-innervating sensory neurons control respiration; however, the physiological significance and molecular mechanisms of these signals remain obscured. Here we show that global and sensory neuron-specific ablation of the mechanically activated ion channel Piezo2 causes respiratory distress and death in newborn mice. Optogenetic activation of Piezo2+ vagal sensory neurons causes apnoea in adult mice. Moreover, induced ablation of Piezo2 in sensory neurons of adult mice causes decreased neuronal responses to lung inflation, an impaired Hering–Breuer mechanoreflex, and increased tidal volume under normal conditions. These phenotypes are reproduced in mice lacking Piezo2 in the nodose ganglion. Our data suggest that Piezo2 is an airway stretch sensor and that Piezo2-mediated mechanotransduction within various airway-innervating sensory neurons is critical for establishing efficient respiration at birth and maintaining normal breathing in adults.