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

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.