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Decrease in activity of smooth muscle L-type Ca2+ channels and its reversal by NF-kappaB inhibitors in Crohn's

Kazuya Kinoshita1, Koichi Sato, Masatoshi Hori

  • 1Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.

American Journal of Physiology. Gastrointestinal and Liver Physiology
|March 21, 2003
PubMed

Insights

Crohn's disease impairs colonic muscle contractions by reducing L-type calcium channel activity, potentially via NF-kappaB pathways. This finding offers insights into gut dysmotility mechanisms in inflammatory bowel disease.

Area of Science:

  • Gastroenterology
  • Physiology
  • Molecular Biology

Background:

  • Crohn's disease is associated with gastrointestinal dysmotility.
  • The precise mechanisms underlying colonic smooth muscle dysfunction in Crohn's disease remain unclear.

Purpose of the Study:

  • To investigate the mechanisms of colonic circular muscle dysmotility in a rat model of Crohn's disease.
  • To identify the role of L-type calcium channels and NF-kappaB signaling in TNBS-induced colitis.

Main Methods:

  • Induction of colitis using 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats.
  • Assessment of colonic circular muscle contractility and L-type calcium channel activity.
  • Analysis of L-type calcium channel mRNA and protein expression.
  • Evaluation of NF-kappaB inhibitors' effects on contractility and channel activity.

Main Results:

  • TNBS-induced colitis significantly decreased contractility in response to KCl, carbachol, and Bay K 8644.
  • L-type calcium channel current density was reduced in TNBS-treated colonic smooth muscle cells, without changes in mRNA or protein expression.
  • NF-kappaB inhibitors partially restored contractility and L-type calcium channel current density.

Conclusions:

  • Decreased L-type calcium channel activity, not altered protein levels, underlies reduced colonic smooth muscle contraction in TNBS-induced colitis.
  • NF-kappaB-dependent pathways likely mediate the dysfunction of L-type calcium channels, contributing to gut dysmotility in Crohn's disease models.

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