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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
Chapter
Part of the Lecture Notes in Computational Vision and Biomechanics book series (LNCVB, volume 10)

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.

Keywords

Irritable Bowel Syndrome Slow Wave Irritable Bowel Syndrome Patient Gastric Electrical Stimulation Voltage Sensor Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Work supported in part by a grant from the NIH (R01 DK52766) (GF) and American Physiological Society Career Enhancement Award (AB).

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Arthur Beyder
    • 1
  • Rachel Lees-Green
    • 2
  • Gianrico Farrugia
    • 1
  1. 1.Enteric Neuroscience Program and Division of Gastroenterology and HepatologyMayo ClinicRochesterUSA
  2. 2.Auckland Bioengineering InstituteThe University of AucklandAucklandNew Zealand

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