Potassium channels in intestinal epithelial cells and their pharmacological modulation: a systematic review

Am J Physiol Cell Physiol. 2021 Apr 1;320(4):C520-C546. doi: 10.1152/ajpcell.00393.2020. Epub 2020 Dec 16.

Abstract

Several potassium channels (KCs) have been described throughout the gastrointestinal tract. Notwithstanding, their contribution to both physiologic and pathophysiologic conditions, as inflammatory bowel disease (IBD), remains underexplored. Therefore, we aim to systematically review, for the first time, the evidence on the characteristics and modulation of KCs in intestinal epithelial cells (IECs). PubMed, Scopus, and Web of Science were searched to identify studies focusing on KCs and their modulation in IECs. The included studies were assessed using a reporting inclusiveness checklist. From the 745 identified records, 73 met the inclusion criteria; their reporting inclusiveness was moderate-high. Some studies described the physiological role of KCs, while others explored their importance in pathological settings. Globally, in IBD animal models, apical KCa1.1 channels, responsible for luminal secretion, were upregulated. In human colonocytes, basolateral KCa3.1 channels were downregulated. The pharmacological inhibition of K2P and Kv influenced intestinal barrier function, promoting inflammation. Evidence suggests a strong association between KCs expression and secretory mechanisms in human and animal IECs. Further research is warranted to explore the usefulness of KC pharmacological modulation as a therapeutic target.

Keywords: K+ channel modulation; intestinal epithelial cells; potassium channels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Cell Line
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Membrane Potentials
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / drug effects*
  • Potassium Channels / metabolism
  • Signal Transduction

Substances

  • Potassium Channel Blockers
  • Potassium Channels