Colitis decreases mechanosensitive K2p channel expression and function in mouse colon sensory neurons

Jun Ho La, G. F. Gebhart

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

TREK-1, TREK-2 and TRAAK are mechanosensitive two-pore domain K+ (K2P) 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 K2P 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 K2P 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 K2P channels and suggest that a decrease in their expression and activities contributes to the increased colon mechanosensitivity that develops in inflammatory bowel conditions.

Original languageEnglish (US)
Pages (from-to)G165-G174
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume301
Issue number1
DOIs
StatePublished - Jul 2011

Keywords

  • Dorsal root ganglia neurons
  • Mechanosensitive channels
  • TREK channels

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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