Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||Acid sensing ion channels 2 and 3 are required for inhibition of visceral nociceptors by benzamil|
|Citation:||Pain, 2007; 133(1-3):150-160|
|Publisher:||Elsevier Science BV|
|Amanda J. Page, Stuart M. Brierley, Christopher M. Martin, Patrick A. Hughes and L. Ashley Blackshaw|
|Abstract:||The Deg/ENaC family of ion channels, including ASIC1, 2 and 3, are candidate mechanotransducers in visceral and somatic sensory neurons, although each channel may play a different role in different sensory pathways. Here we determined which distinct populations of visceral sensory neurons are sensitive to the non-selective Deg/ENaC blocker benzamil, and which ASIC channels are targets for benzamil by studying its actions in knockout mice. Single afferent fiber recordings were made in vitro from mouse high threshold colonic thoracolumbar splanchnic afferents and low threshold gastroesophageal vagal afferents. mRNA expression of ASIC subtypes was compared between colonic and gastroesophageal afferents by quantitative RT-PCR of transcripts following laser capture microdissection of retrogradely labeled cell bodies. Mechanosensitivity of colonic afferents was potently reduced by benzamil (10(-6)-3 x 10(-4)M), whereas gastroesophageal afferents were marginally inhibited. Inhibition of colonic afferent mechanosensitivity by benzamil was markedly diminished in ASIC2-/- and ASIC3-/- mice, but unchanged in ASIC1a-/-. Therefore ASIC2 and 3 are targets for benzamil to inhibit colonic afferent mechanosensitivity. Conversely, gastroesophageal afferents are less sensitive to benzamil, and its action depends less on ASIC expression. mRNA for ASIC3 showed higher and ASIC1a showed lower relative expression in colonic afferents from thoracolumbar dorsal root ganglia than in gastric afferents from nodose (vagal) ganglia. These data indicate that ASICs on colonic afferents present distinct pharmacological targets for visceral pain.|
|Keywords:||Visceral Afferents; Splanchnic Nerves; Vagus Nerve; Mechanoreceptors; Animals; Mice, Knockout; Mice; Amiloride; Sodium Channels; Membrane Proteins; Nerve Tissue Proteins; Action Potentials; Dose-Response Relationship, Drug; Genes; Acid Sensing Ion Channels; In Vitro Techniques|
|Description:||Copyright © 2007 International Association for the Study of Pain Published by Elsevier B.V.|
|Appears in Collections:||Medicine publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.