[P2-3-34] Involvement of TRPV4 channel in water-induced swallowing reflex and SLN-response
Keywords:TRPV4 channels、Water-induced swallowing reflex、Water-induced SLN-response
Water facilitates the triggering of the swallowing reflex. Difficulty in water swallowing is a significant health concern among patients with dysphagia. Understanding the molecular mechanism of the water-induced swallowing reflex is essential to develop therapeutics to overcome the difficulty in water swallowing. Because water is a hypoosmotic stimulus and hypoosmotic stimuli activate transient receptor potential vanilloid 4 (TRPV4) channels, we hypothesize that TRPV4 may be involved in the water-induced swallowing reflex. Experiments were conducted in male Sprague Dawley rats. TRPV4 expression in the superior-laryngeal nerve (SLN)-innervated swallowing-related regions and on the SLN-afferent neurons located in the nodose–petrosal–jugular ganglionic complex (NPJc) was investigated using immunohistochemistry. Reverse transcription polymerase chain reaction (RT-PCR) was conducted to confirm the presence of TRPV4 messenger ribonucleic acid (mRNA) in the NPJc. Swallowing reflexes were identified and counted using high-amplitude electromyogram activity of the mylohyoid muscle and visual checking of laryngeal movements associated with reflex triggering. Water-induced SLN activity was recorded by placing bipolar silver wire electrodes on the unilateral SLN. TRPV4 expression was observed on nerve fibers in the SLN-innervated swallowing-related regions. TRPV4 mRNA expression was observed in the NPJc, and around 25% of SLN-afferent neurons in the NPJc showed TRPV4 immunoreactivity. Prior topical application of a TRPV4 antagonist (RN-9893) to the SLN-innervated swallowing-related regions dose-dependently attenuated the water-induced swallowing reflexes. Additionally, the water-induced SLN activity was significantly reduced by the prior topical application of the TRPV4 antagonist. Our findings suggest that water may activate the TRPV4 channels in the SLN-afferent neurons, thereby generating action potential on the neurons to facilitate the triggering of the swallowing reflex.