Involvement of the epithelial sodium channel in initiation of mechanically evoked swallows in anaesthetized rats

Abstract

Key points Afferents carried by the superior laryngeal nerve play a primary role in the initiation of laryngeal mechanically evoked swallows in anaesthetized rats. Amiloride and its analogues inhibit swallowing evoked by mechanical stimulation, but not swallowing evoked by chemical and electrical stimulation. The epithelial sodium channel is probably involved in the initiation of laryngeal mechanically evoked swallows. Abstract The swallowing reflex plays a critical role in airway protection. Because impaired laryngeal mechanosensation is associated with food bolus aspiration, it is important to know how the laryngeal sensory system regulates swallowing initiation. This study was performed to clarify the neuronal mechanism of mechanically evoked swallows. Urethane‐anaesthetized Sprague–Dawley male rats were used. A swallow was identified by activation of the suprahyoid and thyrohyoid muscles on electromyography. The swallowing threshold was measured by von Frey filament and electrical stimulation of the larynx. The number of swallows induced by upper airway distension and capsaicin application (0.03 nmol, 3 μl) to the vocal folds was counted. The effects of topical application (0.3–30 nmol, 3 μl) of the epithelial sodium channel (ENaC) blocker amiloride and its analogues (benzamil and dimethylamiloride), acid‐sensing ion channel (ASIC) inhibitors (mambalgine‐1 and diminazene) and gadolinium to the laryngeal mucosa on swallowing initiation were evaluated. A nerve transection study indicated that afferents carried by the superior laryngeal nerve play a primary role in the initiation of laryngeal mechanically evoked swallows. The mechanical threshold of swallowing was increased in a dose‐dependent manner by amiloride and its analogues and gadolinium, but not by ASIC inhibitors. The number of swallows by upper airway distension was significantly decreased by benzamil application. However, the initiation of swallows evoked by capsaicin and electrical stimulation was not affected by benzamil application. We speculate that the ENaC is involved in the initiation of laryngeal mechanically evoked swallows.

Sustained laryngeal transient receptor potential vanilloid 1 activation inhibits mechanically induced swallowing in anesthetized rats

“…Electrical stimulation of the recurrent laryngeal nerve evokes the swallowing reflex in rats (31). We previously demonstrated that chemical and mechanical stimulation applied to the vocal folds readily induced the swallowing reflex (36). Although stable mechanical stimulation to the vocal folds was possible throughout the experiment for inducing the swallowing reflex in the present study, the size of the glottis in rats was so small that we could not precisely identify the stimulated location.…”

Evaluation of the association between orofacial pain and dysphagia

“…The swallowing reflex is easily evoked by a variety of stimulations applied to the pharyngeal and laryngeal mucosa. Some ion channels, including TRPV1, TRPA1, and TRPM8, and the epithelial sodium channel are believed to be involved in the initiation of swallowing [16,17,22]. Information is conveyed via the glossopharyngeal and/or vagus nerves to the swallowing central pattern generator (CPG) in the medulla.…”

“…Information is conveyed via the glossopharyngeal and/or vagus nerves to the swallowing central pattern generator (CPG) in the medulla. Among the branches of the glossopharyngeal and vagus nerves, the superior laryngeal nerve (SLN) may have a primary role in initiating the swallowing refl ex [22]. The presence of a unilateral SLN lesion increased the incidence of aspiration in an infant animal model [23], and SLN afferents have important roles in facilitating laryngeal closure based on a human study [24].…”

C. elegans PEZO-1 is a Mechanosensitive Ion Channel Involved in Food Sensation

“…This swallowing motion stems from a constant low-frequency pumping maintained by pharyngeal muscles and bursts of high-frequency pumping from a dedicated pharyngeal nervous system (Avery and Horvitz, 1989; Raizen, Lee and Avery, 1995; Trojanowski, Raizen and Fang-Yen, 2016; Lee et al ., 2017). In mammals, the swallowing reflex is initiated when pressure receptors in the pharynx walls are stimulated by food or liquids, yet the identity of the receptor(s) that directly evoke this mechanical response remain to be identified (Tsujimura et al ., 2019). Interestingly, the Drosophila melanogaster PIEZO ortholog is a mechanosensitive ion channel (Kim et al ., 2012) required for feeding while also avoiding food over-consumption (Min et al ., 2020; Wang et al ., 2020).…”