title: Acid sensitivity of the spinal dorsal root ganglia C-fiber nociceptors innervating the guinea pig esophagus.
abstract: BACKGROUND
  Gastroesophageal reflux can cause high acidity in the esophagus and trigger heartburn and pain. However, because of the esophageal mucosal barrier, the acidity at the nerve terminals of pain-mediating C-fibers in esophageal mucosa is predicted to be substantially lower. We hypothesized that the esophageal dorsal root ganglia (DRG) C-fibers are activated by mild acid (compared to acidic reflux), and express receptors and ion channels highly sensitive to acid.
  
  
  METHODS
  Extracellular single unit recordings of activity originating in esophageal DRG C-fiber nerve terminals were performed in the innervated esophagus preparation ex vivo. Acid was delivered in a manner that bypassed the esophageal mucosal barrier. The expression of mRNA for selected receptors in esophagus-specific DRG neurons was evaluated using single cell RT-PCR.
  
  
  RESULTS
  Mild acid (pH = 6.5-5.5) activated esophageal DRG C-fibers in a pH-dependent manner. The response to mild acid at pH = 6 was not affected by the TRPV1 selective antagonist iodo-resiniferatoxin. The majority (70-95%) of esophageal DRG C-fiber neurons (TRPV1-positive) expressed mRNA for acid sensing ion channels (ASIC1a, ASIC1b, ASIC2b, and/or ASIC3), two-pore-domain (K2P) potassium channel TASK1, and the proton-sensing G-protein coupled receptor OGR1. Other evaluated targets (PKD2L1, TRPV4, TASK3, TALK1, G2A, GPR4, and TDAG8) were expressed rarely.
  
  
  CONCLUSIONS
  Guinea pig esophageal DRG C-fibers are activated by mild acid via a TRPV1-independent mechanism, and express mRNA for several receptors and ion channels highly sensitive to acid. The high acid sensitivity of esophageal C-fibers may contribute to heartburn and pain in conditions of reduced mucosal barrier function.
authors.affiliation: Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: F
authors.initials: F
authors.lastname: Ru
authors.affiliation: Pathophysiology and Gastroenterology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Banovcin
authors.affiliation: Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kollarik
mesh_terms: D062565:Acid Sensing Ion Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004947:Esophagus / Q000187:drug effects* / Q000294:innervation; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D009092:Mucous Membrane; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012996:Solutions / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors
chemical_list: D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D012996:Solutions; D050916:TRPV Cation Channels; C420132:potassium channel subfamily K member 3; D006851:Hydrochloric Acid
keywords: acid sensing; esophagus; nociceptor; pain
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