Role of ion channel mechanosensitivity in the gut: Mechano-electrical feedback exemplified by stretch-dependence of Nav1.5

Arthur Beyder, Rachel Lees-Green, Gianrico Farrugia

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

NaV1.5 is a voltage-gated sodium channel found in the human gastrointestinal tract. In smooth muscle cells (SMC) and interstitial cells of Cajal (ICC), NaV1.5 regulates the resting potential as well as slow wave upstroke and frequency. Mutations in SCN5A, the gene coding for NaV1.5, are associated with gastrointestinal functional disorders. Some patients with irritable bowel syndrome (IBS) have SCN5A mutations that result in functionally abnormal channels. NaV1.5 is mechanosensitive, and some of the mutations associated with gastrointestinal (GI) motility disorders have impaired mechanosensitivity. NaV1.5 mechanosensitivity involves the actin cytoskeleton and associating proteins as well as the lipid bilayer. Mechanical stimulation of NaV1.5 results in an increase in peak current, acceleration of the voltage-dependent activation & inactivation and slowed recovery from inactivation. Biophysical modeling is increasingly used as a tool for investigating the effect of NaV1.5 and other mechanosensitive components in slow wave generation. We summarize the existing models of gastrointestinal cellular electrical activity, and specifically a model of NaV1.5 mechanosensitivity that has been incorporated into one of the cell models. In agreement with the experimental data, mechanical stimulation of NaV1.5 results in increased excitability of the cell model in silico. In this chapter we discuss the current knowledge of the molecular mechanism of NaV1.5 mechanosensitivity, mechano-electrical consequences of NaV1.5 stretch in cells and propose physiologic and pathophysiologic consequences.

Original languageEnglish (US)
Title of host publicationLecture Notes in Computational Vision and Biomechanics
PublisherSpringer Netherlands
Pages7-27
Number of pages21
DOIs
StatePublished - Jan 1 2013

Publication series

NameLecture Notes in Computational Vision and Biomechanics
Volume10
ISSN (Print)2212-9391
ISSN (Electronic)2212-9413

    Fingerprint

Keywords

  • Adapter
  • Arena
  • Constipation
  • Inositol
  • Lidocaine

ASJC Scopus subject areas

  • Signal Processing
  • Biomedical Engineering
  • Mechanical Engineering
  • Computer Vision and Pattern Recognition
  • Computer Science Applications
  • Artificial Intelligence

Cite this

Beyder, A., Lees-Green, R., & Farrugia, G. (2013). Role of ion channel mechanosensitivity in the gut: Mechano-electrical feedback exemplified by stretch-dependence of Nav1.5. In Lecture Notes in Computational Vision and Biomechanics (pp. 7-27). (Lecture Notes in Computational Vision and Biomechanics; Vol. 10). Springer Netherlands. https://doi.org/10.1007/978-94-007-6561-0_2