Transient receptor potential vanilloid 4 channels contribute to the initiation of water-induced swallowing reflexes

The swallowing reflex is essential for the safe transfer of food and liquids from the oral cavity to the esophagus. Water is a strong stimulus for triggering this reflex, yet the molecular mechanisms underlying water-induced activation remain unclear. The aim of this study was to evaluate whether transient receptor potential vanilloid 4 (TRPV4) channels contribute to the water-evoked swallowing reflex. We applied distilled water (DW) or saline to superior laryngeal nerve (SLN)-innervated swallowing-related regions in anesthetized rats, measured swallowing reflexes and SLN activity, and conducted immunohistochemical analyses of TRPV4 expression. DW elicited more frequent swallowing and greater SLN activation than saline. TRPV4 immunoreactivity was observed in epithelial cells, taste bud-like structures, and nerve fibers within the laryngopharyngeal and laryngeal mucosa. DW stimulation also induced c-Fos expression in the nodose-petrosal-jugular ganglionic complex, with ~ 60% of activated neurons coexpressing TRPV4. Pretreatment with the TRPV4 antagonist RN9893 significantly attenuated DW-evoked swallowing and SLN activity. These findings provide integrated physiological, pharmacological, and immunohistochemical evidence that TRPV4 channels contribute as molecular sensors initiating the water-induced swallowing reflex. Our study provides enhanced understanding of TRPV4-mediated sensory regulation of swallowing and suggests that TRPV4 is a potential therapeutic target for oropharyngeal dysphagia.