title: The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function.
abstract: OBJECTIVE
  Visceral mechanoreceptors are critical for perceived sensations and autonomic reflex control of gastrointestinal function. However, the molecular mechanisms underlying visceral mechanosensation remain poorly defined. Degenerin/epithelial Na+ channel (DEG/ENaC) family ion channels are candidate mechanosensory molecules, and we hypothesized that they influence visceral mechanosensation. We examined the influence of the DEG/ENaC channel ASIC1 on gastrointestinal mechanosensory function, on gastric emptying, and on fecal output. We also compared its role in gastrointestinal and somatic sensory function.
  
  
  METHODS
  To assess the role of ASIC1 we studied wild-type and ASIC1-/- mice. Reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis determined expression of ASIC1 messenger RNA and protein in vagal and spinal sensory ganglia. Colonic, gastroesophageal, and cutaneous afferent fibers were characterized by functional subtype and their mechanical stimulus-response relationships were determined. Gastric emptying was determined by using a 13CO2 breath test. Behavioral tests assessed somatic mechanical and thermal sensitivity.
  
  
  RESULTS
  ASIC1 was expressed in sensory ganglia and was lost after disruption of the ASIC1 gene. Loss of ASIC1 increased mechanosensitivity in all colonic and gastroesophageal mechanoreceptor subtypes. In addition, ASIC1-/- mice showed almost double the gastric emptying time of wild-type mice. In contrast, loss of ASIC1 did not affect function in any of the 5 types of cutaneous mechanoreceptors, nor did it affect paw withdrawal responses or fecal output.
  
  
  CONCLUSIONS
  ASIC1 influences visceral but not cutaneous mechanoreceptor function, suggesting that different mechanisms underlie mechanosensory function in gut and skin. The role of ASIC1 is highlighted by prolonging gastric emptying of a meal in ASIC1-/- animals.
authors.affiliation: Nerve-Gut Research Laboratroy, Hanson Institute, Department of Gastroenterology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Page
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Brierley
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Martin
authors.forename: Carlos
authors.initials: C
authors.lastname: Martinez-Salgado
authors.forename: John A
authors.initials: JA
authors.lastname: Wemmie
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Brennan
authors.forename: Erin
authors.initials: E
authors.lastname: Symonds
authors.forename: Taher
authors.initials: T
authors.lastname: Omari
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
authors.forename: L Ashley
authors.initials: LA
authors.lastname: Blackshaw
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D001944:Breath Tests; D002245:Carbon Dioxide / Q000032:analysis; D004068:Digestive System Physiological Phenomena; D005247:Feeding Behavior; D005746:Gastric Emptying / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008465:Mechanoreceptors / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*
chemical_list: C568266:ASIC1 protein, human; C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D002245:Carbon Dioxide