Chemical receptors of the arytenoid: A comparison of human and mouse

Abstract

Objectives/Hypothesis The larynx is a highly responsive organ exposed to mechanical, thermal, and chemical stimuli. Chemicals elicit responses both in intraepithelial nerve fibers and in specialized chemosensory cells, including scattered solitary cells as well as taste cells organized into taste buds. Activation of both chemosensory cells and taste buds in the larynx elicit cough, swallow, or apnea with exposure to sour or bitter substances, and even by water or sweet‐tasting chemicals. In an effort to begin understanding their function, we sought to compare the distribution, density, and types of chemosensory cells and chemoresponsive nerve fibers in laryngeal epithelium of humans and mice. Study Design Animal and human laboratory analysis. Methods Using immunohistochemistry, we identified taste cells and polymodal nociceptive nerve fibers in the arytenoid area of the laryngeal epithelium of the following: 1) infants undergoing supraglottoplasty for laryngomalacia, and 2) a cadaveric specimen procured from a 34‐year‐old donor. We then compared these findings to both preweanling and mature mouse tissue. Results Arytenoid tissue from both human and mouse contained many taste buds containing type II taste cells—bitter, sweet, or umami sensing—which were innervated by nerve fibers expressing P2X3 type adenosine triphosphate receptors. Type III cells (acid responsive) were also present, but they were fewer in human tissue than in equivalent tissue from mice. In both species, the epithelium was densely innervated by free nerve endings. Conclusions Our findings suggest that from a standpoint of chemosensation, human and mouse larynges are biologically similar. This suggests that a murine model can be used effectively in laryngeal chemosensory research. Level of Evidence NA Laryngoscope, 130:423–430, 2020

An Airway Protection Program Revealed by Sweeping Genetic Control of Vagal Afferents

“…Because mouse sensory neurons can detect laryngeal stimuli that evoke cough in other species, one model is that sensory pathways for airway threats such as those described here are evolutionarily conserved between mouse and human, even if evoked motor programs have diverged. Consistent with this model, human and mouse contain a similar diversity of laryngeal taste cells (Jetté et al, 2020). It is thus intriguing to note that we observed ll 586 Cell 181, 574-589, April 30, 2020 Article a loss of physiological responses to laryngeal water perfusion in P2x2/P2x3 knockout mice.…”

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“… Afferents from the carotid body and from the posterior third of the tongue run together in the glossopharyngeal nerve through the petrosal ganglion to reach the solitary tract nucleus [ 55 ], targeting partially overlapping areas in the brainstem. Functionally, in taste buds, there are receptors sensitive to pH (sour taste receptors) that act similarly to ectopic chemoreceptors present in the larynx [ 56 ] and, most interestingly, in the carotid body [ 57 ]. Receptors for carbon dioxide are also present in the olfactory mucosa [ 58 ] and in the mouth [ 59 ].…”

“…Functionally, in taste buds, there are receptors sensitive to pH (sour taste receptors) that act similarly to ectopic chemoreceptors present in the larynx [ 56 ] and, most interestingly, in the carotid body [ 57 ].…”

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“…84 Receptors include several from the transient receptor potential (TRP) family of receptors (TRPV1, TRPA, and TRPV4), purinergic receptors (e.g., P3 × 3), stretch/mechanoreceptors (rapidly adapting/slow-adapting receptors), and nociceptive C-fiber receptors. 84,85 Receptor activators include heat and cold, protons, capsaicin, menthol, adrenaline, and mechanical stretch. 84 As many stimuli converge to initiate one reflex arc, there may be a reinforcing or converging effect.…”