# Mechanism of action of gastric Interstitial cells of Cajal

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 2022 · $509,851

## Abstract

Summary
The stomach is a miraculous organ that can accept large volumes of food and then grind up solids to make
nutrients absorbable in the small intestine. Unfortunately some patients find eating, a palpable joy of living, an
uncomfortable or painful experience. Functional disorders of gastric motility plague the lives of these patients
and therapies are out of reach because the basic mechanisms of gastric motility are unknown. New techniques
allow monitoring of the pacemaker activity that fuels gastric peristalsis and gastric emptying, and this project
proposes to utilize cutting-edge approaches to better understand basic mechanisms of gastric motility. Three
specific aims will be pursued: i) Characterize the relationship between Ca2+ signaling patterns and pacemaker
activity in interstitial cells of Cajal (ICC-MY and ICC-IM) of the mouse and human gastric corpus and antrum; ii)
Compare molecular and functional characteristics of the pacemakersomes in mouse and human corpus and
aims will investigate the basic cellular behaviors that generate pacemaker activity ICC-MY and ICC-IM using
optogenetic and electrophysiological techniques to monitor pacemaker activity of ICC in situ. Preliminary data
suggest that Ca2+ transients underlie the electrical responses known as slow waves that power gastric peristalsis.
The basis for the corpus-to-antrum frequency gradient will be explored and concepts about why corpus frequency
exceeds antral frequency will be investigated. The basis for propagation of slow waves in ICC networks will be
investigated and the mechanisms responsible for integrated organization of pacemaker activity will be
determined. Optogenetics provides the opportunity to study the pattern of ICC activation in intact gastric muscles
and the intact stomach. Preliminary data reveals a novel pattern of slow wave activation never previously
observed with extracellular electrical recording. We will also investigate how enteric motor neural inputs and
other chronotropic mediators regulate gastric slow waves and how application of chronotropic stimuli affects the
pattern of slow wave propagation in the stomach.
OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020)Page Continuation Format Page

## Key facts

- **NIH application ID:** 10472002
- **Project number:** 5R01DK057236-16
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** KENTON M SANDERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $509,851
- **Award type:** 5
- **Project period:** 2000-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10472002

## Citation

> US National Institutes of Health, RePORTER application 10472002, Mechanism of action of gastric Interstitial cells of Cajal (5R01DK057236-16). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10472002. Licensed CC0.

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