title: Colitis decreases mechanosensitive K2P channel expression and function in mouse colon sensory neurons.
abstract: TREK-1, TREK-2 and TRAAK are mechanosensitive two-pore domain K(+) (K(2P)) channels thought to be involved in the attenuation of mechanotransduction. Because colon inflammation is associated with colon mechanohypersensitivity, we hypothesized that the role of these channels in colon sensory (dorsal root ganglion, DRG) neurons would be reduced by colon inflammation. Accordingly, we studied the functional expression of mechanosensitive K(2P) channels in colon sensory neurons in both thoracolumbar (TL) and lumbosacral (LS) DRG that represent the splanchnic and pelvic nerve innervations of the colon, respectively. In colon DRG neurons identified by retrograde tracer previously injected into the colon wall, 62% of TL neurons and 83% of LS neurons expressed at least one of three K(2P) channel mRNAs; the proportion of neurons expressing the TREK-1 gene was greater in LS than in TL DRG. In electrophysiological studies, single-channel activities of TREK-1a, TREK-1b, TREK-2, and TRAAK-like channels were detected in cultured colon DRG neuronal membranes. After trinitrobenzene sulfonic acid-induced colon inflammation, we observed significant decreases in the amount of TREK-1 mRNA, in the response of TREK-2-like channels to membrane stretch, and in the whole cell outward current during osmotic stretch in LS colon DRG neurons. These findings document that the majority of DRG neurons innervating the mouse colon express mechanosensitive K(2P) channels and suggest that a decrease in their expression and activities contributes to the increased colon mechanosensitivity that develops in inflammatory bowel conditions.
authors.affiliation: Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pennsylvania, USA. laj@upmc.edu
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: La
authors.forename: G F
authors.initials: GF
authors.lastname: Gebhart
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000294:innervation / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D008297:Male; D040542:Mechanotransduction, Cellular; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*; D013153:Splanchnic Nerves / Q000378:metabolism / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
chemical_list: C503445:Kcnk10 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D014302:Trinitrobenzenesulfonic Acid