Airway mechanoreceptors that control breathing

Abstract

The airways contain a myriad of sensory cells that mediate olfaction, control breathing, and protect the respiratory system from damage and disease. The vagus nerve is a major conduit between lung and brain required for normal respiration, and some vagal sensory neurons detect airway expansion that occurs with every breath. Mechanical inflation of the lungs and airways triggers a protective respiratory reflex termed the Hering‐Breuer inspiratory reflex, characterized by acute apnea. How vagal sensory neurons detect increases in airway volume was unknown at a molecular level. We initiated a molecular and genetic analysis of the sensory vagus nerve, identifying cell types that innervate the lung and powerfully control breathing. Moreover, we identified a critical role for the ion channel Piezo2 in airway mechanoreception. Optogenetic activation of vagal afferents containing Piezo2 causes apnea, trapping animals in a state of exhalation. Moreover, conditional deletion of Piezo2 from nodose ganglion‐derived sensory neurons eliminates sensory neuron responses to airway stretch as well as the classical Hering‐Breuer inspiratory reflex. These findings indicate a key role for Piezo2 as an airway stretch sensor critical for establishing efficient respiration at birth and maintaining respiratory homeostasis in adults. Understanding the sensory biology of respiratory control neurons in the vagus nerve may provide therapeutic targets for airway disease intervention.Support or Funding InformationHarvard‐MIT Joint Research Grants Program in Basic Neuroscience to S.D.L, R01DE022358 to A.P. and R01HL132255, and a Giovanni Armenise‐Harvard Foundation Grant to S.D.L. A.P. is an investigator of the Howard Hughes Medical Institute.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.