Role of epithelial ion transports in inflammatory bowel disease

Am J Physiol Gastrointest Liver Physiol. 2016 Apr 1;310(7):G460-76. doi: 10.1152/ajpgi.00369.2015. Epub 2016 Jan 7.

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na(+)-K(+)-ATPase (NKA), Na(+)/H(+) exchangers (NHEs), epithelial Na(+) channels (ENaC), and K(+) channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.

Keywords: K+ channels; Na+-K+-ATPase; Na+/H+ exchangers; epithelial Na+ channels; inflammatory bowel disease.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Epithelial Cells / drug effects
  • Epithelial Cells / enzymology*
  • Epithelial Sodium Channels / drug effects
  • Epithelial Sodium Channels / metabolism*
  • Gastrointestinal Absorption
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / enzymology*
  • Inflammatory Bowel Diseases / physiopathology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / enzymology*
  • Intestinal Mucosa / physiopathology
  • Ion Transport
  • Membrane Transport Modulators / therapeutic use
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Signal Transduction
  • Sodium-Hydrogen Exchangers / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism*

Substances

  • Epithelial Sodium Channels
  • Gastrointestinal Agents
  • Membrane Transport Modulators
  • Potassium Channels
  • Sodium-Hydrogen Exchangers
  • Sodium-Potassium-Exchanging ATPase