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Erschienen in:
New Advances in Gastrointestinal Motility Research Kapitel lesen Erstes Kapitel lesen

2013 | OriginalPaper | Buchkapitel

Role of Ion Channel Mechanosensitivity in the Gut: Mechano-Electrical Feedback Exemplified By Stretch-Dependence of Nav1.5

verfasst von : Arthur Beyder, Rachel Lees-Green, Gianrico Farrugia

Erschienen in: New Advances in Gastrointestinal Motility Research

Verlag: Springer Netherlands

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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.

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Vorheriges Kapitel New Advances in Gastrointestinal Motility Research
Nächstes Kapitel ICC Network Density: Regulation and Consequences
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Metadaten
Titel
Role of Ion Channel Mechanosensitivity in the Gut: Mechano-Electrical Feedback Exemplified By Stretch-Dependence of Nav1.5
verfasst von
Arthur Beyder
Rachel Lees-Green
Gianrico Farrugia
Copyright-Jahr
2013
Verlag
Springer Netherlands
Buch
New Advances in Gastrointestinal Motility Research

Print ISBN: 978-94-007-6560-3

Electronic ISBN: 978-94-007-6561-0

Copyright-Jahr: 2013

DOI
https://doi.org/10.1007/978-94-007-6561-0_2

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