title: Trinitrobenzenesulphonic acid colitis alters Na 1.8 channel expression in mouse dorsal root ganglia neurons.
abstract: Visceral inflammation evokes hyperexcitability in nociceptive dorsal root ganglia (DRG) neurons and these changes are associated with increased voltage-gated sodium channel (Na(v)) 1.8 current density, but the molecular determinants of these changes are unclear. This study used Western blotting to measure changes in Na(v) 1.7, 1.8 and 1.9 protein expression during trinitrobenzenesulphonic acid (TNBS) colitis and quantitative polymerase chain reaction (PCR) to examine corresponding changes in mRNA. Colonic neurons were labelled with the retrograde tracer Fast Blue injected into the wall of the distal colon and quantitative PCR performed on laser-captured labelled colonic neurons from ganglia at T9-13 or unlabelled DRG neurons from the upper spinal cord. Immunohistochemistry and western blots were performed on whole DRG from the same sites. Fast Blue-labelled neurons demonstrated Na(v) 1.7, 1.8 and 1.9 immunoreactivity. On day 7 of colitis, which correlated with electrophysiological studies, there was a threefold increase in Na(v) 1.8 protein in ganglia from T9 to 13, but Na(v) 1.7 and 1.9 levels were unchanged. There was no corresponding change in the Na(v) 1.8 alpha-subunit mRNA levels. However, on days 2 and 4, Na(v) 1.8 mRNA was decreased 10-fold. Na(v) 1.8 protein and mRNA levels were unchanged in neurons isolated from ganglia in the upper spinal cord, where colonic neurons are not found. These findings suggest that the TNBS evoked increase in Na(v) 1.8 currents is associated with increased numbers of channels. The absence of corresponding changes in transcript suggests a translational or post-translational mechanism, but the 10-fold recovery of transcript preceding this time point also demonstrates a complex transcriptional regulation.
authors.affiliation: Kingston General Hospital, Queen's University, ON, Canada.
authors.forename: D E
authors.initials: DE
authors.lastname: King
authors.forename: R J
authors.initials: RJ
authors.lastname: Macleod
authors.forename: S J
authors.initials: SJ
authors.lastname: Vanner
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000503:physiopathology; D003106:Colon / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D005727:Ganglia, Spinal / Q000166:cytology*; D051379:Mice; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; D021122:Protein Subunits; C568318:Scn10a protein, mouse; C491885:Scn11a protein, mouse; D015222:Sodium Channels; D014302:Trinitrobenzenesulfonic Acid