Journal article
The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function
Gastroenterology (New York, N.Y. 1943), Vol.127(6), pp.1739-1747
2004
DOI: 10.1053/j.gastro.2004.08.061
PMID: 15578512
Abstract
Background & Aims:
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
13CO
2 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.
Details
- Title: Subtitle
- The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function
- Creators
- Amanda J Page - Nerve-Gut Research Laboratory, Hanson Institute, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, AustraliaStuart M Brierley - Nerve-Gut Research Laboratory, Hanson Institute, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, AustraliaChristopher M Martin - Nerve-Gut Research Laboratory, Hanson Institute, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, AustraliaCarlos Martinez-Salgado - Growth Factors and Regeneration Group, Max-Delbrück Center for Molecular Medicine, Berlin-Buch, GermanyJohn A Wemmie - Department of Psychiatry, University of Iowa College of Medicine, Iowa City, Iowa, USATimothy J Brennan - Department of Anesthesia, University of Iowa College of Medicine, Iowa City, Iowa, USAErin Symonds - Centre for Paediatric and Adolescent Gastroenterology, Women’s and Children’s Hospital, North Adelaide, AustraliaTaher Omari - Department of Medicine, University of Adelaide, Adelaide, AustraliaGary R Lewin - Growth Factors and Regeneration Group, Max-Delbrück Center for Molecular Medicine, Berlin-Buch, GermanyMichael J Welsh - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USAL. Ashley Blackshaw - Nerve-Gut Research Laboratory, Hanson Institute, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, Australia
- Resource Type
- Journal article
- Publication Details
- Gastroenterology (New York, N.Y. 1943), Vol.127(6), pp.1739-1747
- Publisher
- Elsevier Inc
- DOI
- 10.1053/j.gastro.2004.08.061
- PMID
- 15578512
- ISSN
- 0016-5085
- eISSN
- 1528-0012
- Language
- English
- Date published
- 2004
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Anesthesia; Neurosurgery; Internal Medicine
- Record Identifier
- 9984066132302771
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