The vagal motor fibers innervating the esophageal striated muscle are essential for esophageal motility including swallowing and vomiting. However, it is unknown which subtypes of voltage-gated sodium channels (NaV1s) regulate action potential conduction in these efferent nerve fibers. The information on the NaV1s subtypes is necessary for understanding their potential side effects on upper gut, as novel inhibitors of NaV1s are developed for treatment of pain. We used isolated superfused (35 °C) vagally-innervated mouse esophagus striated muscle preparation (mucosa removed) to measure isometric contractions of circular striated muscle evoked by electrical stimulation of the vagus nerve. NaV1 inhibitors were applied to the de-sheathed segment of the vagus nerve. Tetrodotoxin (TTX) applied to the vagus nerve completely abolished electrically evoked contractions. The selective NaV1.7 inhibitor PF-05089771 alone partially inhibited contractions and caused a >3-fold rightward shift in the TTX concentration-inhibition curve. The NaV1.1, NaV1.2 and NaV1.3 group inhibitor ICA-121431 failed to inhibit contractions, or to alter TTX concentration-inhibition curves in the absence or in the presence of PF-05089771. RT-PCR indicated lack of NaV1.4 expression in nucleus ambiguus and dorsal motor nucleus of the vagus nerve, which contain motor and preganglionic neurons projecting to the esophagus. We conclude that the action potential conduction in the vagal motor fibers to the esophageal striated muscle in the mouse is mediated by TTX-sensitive voltage gated sodium channels including NaV1.7 and most probably NaV1.6. The role of NaV1.6 is supported by ruling out other TTX-sensitive NaV1s (NaV1.1-1.4) in the NaV1.7-independent conduction.

• MeSH
• akční potenciály MeSH
• elektrická stimulace MeSH
• ezofágus inervace   MeSH
• motorické neurony fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nervus vagus fyziologie   MeSH
• příčně pruhované svaly inervace   MeSH
• sodíkové kanálky řízené napětím genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• sodíkové kanálky řízené napětím MeSH

Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing.Upper airway cough syndrome (UACS) - previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.

• MeSH
• chronická nemoc MeSH
• kapsaicin škodlivé účinky   MeSH
• kašel chemicky indukované   patofyziologie   MeSH
• kationtové kanály TRPV agonisté   fyziologie   MeSH
• kationtový kanál TRPA1 agonisté   fyziologie   MeSH
• lidé MeSH
• nervové receptory účinky léků   fyziologie   MeSH
• nervus vagus účinky léků   patofyziologie   MeSH
• nosní sliznice účinky léků   patofyziologie   MeSH
• syndrom MeSH
• trachea účinky léků   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kapsaicin MeSH
• kationtové kanály TRPV MeSH
• kationtový kanál TRPA1 MeSH
• TRPA1 protein, human MeSH Prohlížeč
• TRPV1 protein, human MeSH Prohlížeč