Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/27514
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dc.contributor.authorPage, A.en
dc.contributor.authorBrierley, S.en
dc.contributor.authorMartin, C.en
dc.contributor.authorPrice, M.en
dc.contributor.authorSymonds, E.en
dc.contributor.authorButler, R.en
dc.contributor.authorWemmie, J.en
dc.contributor.authorBlackshaw, L.en
dc.date.issued2005en
dc.identifier.citationGut, 2005; 54(10):1408-1415en
dc.identifier.issn0017-5749en
dc.identifier.issn1468-3288en
dc.identifier.urihttp://hdl.handle.net/2440/27514-
dc.description.abstract<h4>Aims</h4>Members of the acid sensing ion channel (ASIC) family are strong candidates as mechanical transducers in sensory function. The authors have shown that ASIC1a has no role in skin but a clear influence in gastrointestinal mechanotransduction. Here they investigate further ASIC1a in gut mechanoreceptors, and compare its influence with ASIC2 and ASIC3.<h4>Methods and results</h4>Expression of ASIC1a, 2, and 3 mRNA was found in vagal (nodose) and dorsal root ganglia (DRG), and was lost in mice lacking the respective genes. Recordings of different classes of splanchnic colonic afferents and vagal gastro-oesophageal afferents revealed that disruption of ASIC1a increased the mechanical sensitivity of all afferents in both locations. Disruption of ASIC2 had varied effects: increased mechanosensitivity in gastro-oesophageal mucosal endings, decreases in gastro-oesophageal tension receptors, increases in colonic serosal endings, and no change in colonic mesenteric endings. In ASIC3-/- mice, all afferent classes had markedly reduced mechanosensitivity except gastro-oesophageal mucosal receptors. Observations of gastric emptying and faecal output confirmed that increases in mechanosensitivity translate to changes in digestive function in conscious animals.<h4>Conclusions</h4>These data show that ASIC3 makes a critical positive contribution to mechanosensitivity in three out of four classes of visceral afferents. The presence of ASIC1a appears to provide an inhibitory contribution to the ion channel complex, whereas the role of ASIC2 differs widely across subclasses of afferents. These findings contrast sharply with the effects of ASIC1, 2, and 3 in skin, suggesting that targeting these subunits with pharmacological agents may have different and more pronounced effects on mechanosensitivity in the viscera.en
dc.language.isoenen
dc.publisherBritish Med Journal Publ Groupen
dc.subjectGastrointestinal Tract; Intestinal Mucosa; Colon; Esophagus; Stomach; Ganglia, Sensory; Vagus Nerve; Mechanoreceptors; Spinal Nerves; Animals; Mice; Sodium Channels; Membrane Proteins; Nerve Tissue Proteins; RNA, Messenger; Electrophysiology; Adaptation, Physiological; Defecation; Gastric Emptying; Acid Sensing Ion Channelsen
dc.titleDifferent contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory functionen
dc.typeJournal articleen
dc.identifier.rmid0020050517en
dc.identifier.doi10.1136/gut.2005.071084en
dc.identifier.pubid54988-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidPage, A. [0000-0002-7086-5865]en
dc.identifier.orcidBrierley, S. [0000-0002-2527-2905]en
dc.identifier.orcidBlackshaw, L. [0000-0003-1565-0850]en
Appears in Collections:Molecular and Biomedical Science publications

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