The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function.
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.
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Amanda J
AJ
Nerve-Gut Research Laboratroy, Hanson Institute, Department of Gastroenterology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
Brierley
Stuart M
SM
Martin
Christopher M
CM
Martinez-Salgado
Carlos
C
Wemmie
John A
JA
Brennan
Timothy J
TJ
Symonds
Erin
E
Omari
Taher
T
Lewin
Gary R
GR
Welsh
Michael J
MJ
Blackshaw
L Ashley
LA
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*
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