Prostaglandin E 2 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 E 2 (PGE 2 ) increases in the lungs and airways. PGE 2 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 PGE 2 ‐induced sensitization of pulmonary C neurones. We used the perforated patch‐clamp technique to study the effects of PGE 2 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. PGE 2 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 PGE 2 . We conclude that these modulatory effects of PGE 2 on TTX‐R I Na play an important role in the sensitization of pulmonary C neurones.