Prostaglandin E₂ potentiates a TTX-resistant sodium current in rat capsaicin-sensitive vagal pulmonary sensory neurones

Capsaicin-sensitive vagal pulmonary neurones (pulmonary C neurones) play an important role in regulating airway function. During airway inflammation, the level of prostaglandin E₂ (PGE₂) increases in the lungs and airways. PGE₂ has been shown to sensitize isolated pulmonary C neurones. The somatosensory correlate of the pulmonary C neurone, the small-diameter nociceptive neurone of the dorsal root ganglion, contains a high percentage of tetrodotoxin-resistant sodium currents (TTX-R I_Na). Therefore, this study was carried out to determine whether these channel currents are involved in the PGE₂-induced sensitization of pulmonary C neurones. We used the perforated patch-clamp technique to study the effects of PGE₂ on the TTX-R I_Na in acutely cultured capsaicin-sensitive pulmonary neurones that were identified by retrograde labelling with a fluorescent tracer, DiI. We found that the pulmonary neurones sensitive to capsaicin had a higher percentage of TTX-R I_Na than that of capsaicin-insensitive pulmonary neurones. PGE₂ exposure increased the evoked TTX-R I_Na when experiments were performed at both room temperature and at 37°C. Furthermore, stimulation of the adenylyl cyclase/protein kinase A pathway with either forskolin or Sp-5,6-DCl-cBiMPS potentiated the TTX-R I_Na in a manner similar to that of PGE₂. We conclude that these modulatory effects of PGE₂ on TTX-R I_Na play an important role in the sensitization of pulmonary C neurones.