P2X2 receptors differentiate placodal vs. neural crest C-fiber phenotypes innervating guinea pig lungs and esophagus

Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L858-65. doi: 10.1152/ajplung.90360.2008. Epub 2008 Aug 8.


The lungs and esophagus are innervated by sensory neurons with somata in the nodose, jugular, and dorsal root ganglion. These sensory ganglia are derived from embryonic placode (nodose) and neural crest tissues (jugular and dorsal root ganglia; DRG). We addressed the hypothesis that the neuron's embryonic origin (e.g., placode vs. neural crest) plays a greater role in determining particular aspects of its phenotype than the environment in which it innervates (e.g., lungs vs. esophagus). This hypothesis was tested using a combination of extracellular and patch-clamp electrophysiology and single-cell RT-PCR from guinea pig neurons. Nodose, but not jugular C-fibers innervating the lungs and esophagus, responded to alpha,beta-methylene ATP with action potential discharge that was sensitive to the P2X3 (P2X2/3) selective receptor antagonist A-317491. The somata of lung- and esophagus-specific sensory fibers were identified using retrograde tracing with a fluorescent dye. Esophageal- and lung-traced neurons from placodal tissue (nodose neurons) responded similarly to alpha,beta-methylene ATP (30 microM) with a large sustained inward current, whereas in neurons derived from neural crest tissue (jugular and DRG neurons), the same dose of alpha,beta-methylene ATP resulted in only a transient rapidly inactivating current or no detectable current. It has been shown previously that only activation of P2X2/3 heteromeric receptors produce sustained currents, whereas homomeric P2X3 receptor activation produces a rapidly inactivating current. Consistent with this, single-cell RT-PCR analysis revealed that the nodose ganglion neurons innervating the lungs and esophagus expressed mRNA for P2X2 and P2X3 subunits, whereas the vast majority of jugular and dorsal root ganglia innervating these tissues expressed only P2X3 mRNA with little to no P2X2 mRNA expression. We conclude that the responsiveness of C-fibers innervating the lungs and esophagus to ATP and other purinergic agonists is determined more by their embryonic origin than by the environment of the tissue they ultimately innervate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Capsaicin / pharmacology
  • Esophagus / cytology
  • Esophagus / innervation*
  • Esophagus / metabolism
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Gene Expression Regulation / drug effects
  • Guinea Pigs
  • Ion Channel Gating / drug effects
  • Lung / cytology
  • Lung / innervation*
  • Lung / metabolism
  • Male
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / metabolism*
  • Neural Crest / cytology
  • Neural Crest / drug effects
  • Neural Crest / metabolism*
  • Nodose Ganglion / drug effects
  • Nodose Ganglion / metabolism
  • Organ Specificity / drug effects
  • Phenotype
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism


  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X2
  • Adenosine Triphosphate
  • alpha,beta-methyleneadenosine 5'-triphosphate
  • Capsaicin