# Molecular basis for mechanosensitivity of esophageal enteric neurons (EMN)

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2020 · —

## Abstract

Introduction: Impaired lower esophageal sphincter (LES) relaxation is the hallmark of achalasia esophagus
and spastic motor disorders of the esophagus. On the other hand, excessive LES relaxation (transient LES
relaxation) leads to reflux disease. Therefore, LES dysfunction contributes to significant morbidity and health
related costs. Our current understanding is that the LES relaxation is neurogenic, mediated by vagus nerve
which synapses with the inhibitory motor neurons of the myenteric plexus. Hypothesis: Our hypothesis is that
the vagus nerve synapse with the excitatory nerves of the longitudinal muscles of the esophagus and it is the
mechanical stretch caused by longitudinal muscle contraction that activates inhibitory motor neurons located in
the myenteric plexus through a mechanosensitive (stretch-sensitive) mechanism. We will identify the molecular
candidates for the mechanosensitive property of the myenteric neurons. Aim: The specific goals of our
studies are: 1).To examine TRPV4 as a mechanosensitive molecule of the esophageal myenteric neurons
(EMN); 2). To examine NCX1 as a mechanosensitive molecule of the EMN; 3).To determine if TRPV4 and
NCX1 are synergistic in the mechanosensitivity of the EMN.
Clinical Relationships: A large number of veterans suffer from reflux disease and spastic motor disorders of
the esophagus and we believe that LES dysfunction plays a major role in both of the above. A better
understanding of the neural control of esophageal peristalsis and LES relaxation is likely to lead to better
treatment strategies in various esophageal motor disorders. Impact/Significance: We hope that an improved
understanding of the mechanism of central and peripheral control of esophagus and LES motor function will
results in better strategies to treat reflux disease and spastic disorders of the esophagus.

## Key facts

- **NIH application ID:** 9979761
- **Project number:** 5I01BX000149-11
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** RAVINDER K. MITTAL
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2009-04-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979761

## Citation

> US National Institutes of Health, RePORTER application 9979761, Molecular basis for mechanosensitivity of esophageal enteric neurons (EMN) (5I01BX000149-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979761. Licensed CC0.

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