Cholinergic chemosensory cells in the trachea regulate breathing

Area of Science:

• Pulmonology
• Neuroscience
• Cell Biology

Background:

• Lower airway epithelium contains brush cells with unknown function, characterized by apical microvilli.
• Similar cells in the nose act as solitary chemosensory cells, triggering trigeminal reflexes.
• The sensory role of tracheal brush cells remains uncharacterized.

Purpose of the Study:

• To investigate the function of brush cells in the mouse trachea.
• To determine if tracheal brush cells function as chemosensory receptors.
• To elucidate the role of brush cells in the regulation of respiration.

Main Methods:

• Analysis of gene and protein expression in mouse tracheal brush cells.
• Application of agonists for bitter taste receptors and nicotinic acetylcholine receptors.
• Measurement of respiratory rate changes in response to chemical stimuli and receptor blockade.

Main Results:

• Tracheal brush cells express bitter taste receptors (Tas2R105, Tas2R108) and downstream signaling molecules (α-gustducin, phospholipase C(β2)).
• Brush cells synthesize acetylcholine and are innervated by vagal sensory fibers expressing nicotinic acetylcholine receptors.
• Stimulation of these receptors reduced breathing frequency, an effect blocked by nicotinic receptor antagonists.

Conclusions:

• Tracheal brush cells are cholinergic sensors of the lower airway luminal environment.
• These cells detect chemical stimuli, likely bitter compounds, via taste receptors.
• Brush cells directly influence respiratory regulation through vagal nerve pathways.