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

摘要

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 INa). 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 INa 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 INa than that of capsaicin-insensitive pulmonary neurones. PGE2 exposure increased the evoked TTX-R INa 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 INa in a manner similar to that of PGE2. We conclude that these modulatory effects of PGE2 on TTX-R INa play an important role in the sensitization of pulmonary C neurones.