PIEZO2-mediated mechanosensation controls breathing patterns

抄録

Respiratory organs experience repetitive and wide-ranging mechanical forces during breathing. Some of those mechanical signals are transduced by airway-innervating sensory neurons and control respiration; however, the physiological significance and molecular mechanisms of these signals remained obscure. PIEZO2, a mechanically activated cation channel, is the principal mechanotransducer in low-threshold cutaneous mechanoreceptors and skeletal-muscle-innervating proprioceptors in mice. We found that global and sensory neuron-specific ablation of PIEZO2 causes respiratory distress and death in newborn mice. Optogenetic activation of PIEZO2 expressing vagal sensory neurons causes apnoea in adult mice. Moreover, induced ablation of PIEZO2 in nodose sensory neurons of adult mice causes decreased neuronal responses to lung inflation, an impaired Hering-Breuer mechanoreflex, and increased tidal volume under normal conditions. Our data suggest that PIEZO2 is an airway stretch sensor and that PIEZO2-mediated mechanotransduction within airway-innervating sensory neurons is critical for establishing efficient respiration at birth and maintaining normal breathing in adults.