title: Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels.
abstract: BACKGROUND
  The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1) and ASIC3 (acid sensing ion channel-3) respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively.
  
  
  METHODS
  The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons), and their soma diameter was measured.
  
  
  RESULTS
  Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative) were significantly more frequent among pleural (35%) than pulmonary afferents (20%). TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung) and 48% (pleura) of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive).
  
  
  CONCLUSIONS
  Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli.
authors.affiliation: Institute for Anatomy and Cell Biology, University of Giessen Lung Center, Justus-Liebig-University, Giessen, Germany. Migro@gmx.de
authors.forename: Michael
authors.initials: M
authors.lastname: Groth
authors.forename: Tanja
authors.initials: T
authors.lastname: Helbig
authors.forename: Veronika
authors.initials: V
authors.lastname: Grau
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
authors.forename: Rainer V
authors.initials: RV
authors.lastname: Haberberger
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D002232:Carbocyanines; D048429:Cell Size; D005260:Female; D005456:Fluorescent Dyes; D005727:Ganglia, Spinal / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000294:innervation*; D008565:Membrane Proteins / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D016900:Neurofilament Proteins / Q000032:analysis; D009475:Neurons, Afferent / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D010994:Pleura / Q000294:innervation*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000032:analysis*; D050916:TRPV Cation Channels / Q000032:analysis*
chemical_list: C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D002232:Carbocyanines; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C066858:neurofilament protein NF 68; C024286:3,3'-dioctadecylindocarbocyanine