Author: ["Keiko Nonomura","Seung-Hyun Woo","Rui B. Chang","Astrid Gillich","Zhaozhu Qiu","Allain G. Francisco","Sanjeev S. Ranade","Stephen D. Liberles","Ardem Patapoutian"]
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Abstract
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. The mechanoreceptor Piezo2 is required for both the Hering–Breuer inflation reflex in adult mice and the inflation of the lungs of newborn mice. The Hering–Breuer inflation reflex, described some 150 years ago, is thought to protect the lung from overinflation thanks to stretch-activated sensory neurons that innervate the lung, but the actual molecular and cellular mechanisms involved have remained unknown. Ardem Patapoutian and colleagues find that this reflex is absent in adult mice that lack the mechanosensitive ion channel Piezo2, which was previously implicated in the skin's sense of touch. Surprisingly, Piezo2 is also required for initial lung inflation at birth, thus establishing a role for mechanotransduction in respiratory control in both newborn and adult mice.Cite this article
Nonomura, K., Woo, SH., Chang, R. et al. Piezo2 senses airway stretch and mediates lung inflation-induced apnoea. Nature 541, 176–181 (2017). https://doi.org/10.1038/nature20793 