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 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 degrees 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.
Kwong
Kevin
K
Department of Physiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Lee
Lu-Yuan
LY
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
D015222:Sodium Channels; D013779:Tetrodotoxin; D015232:Dinoprostone; D002211:Capsaicin