# Role of interstitial cells of Cajal in patterned colonic motor activity

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 2024 · $591,987

## Abstract

Summary
Colonic motility is the product of myogenic and neurogenic factors that regulate the excitability of smooth muscle
cells (SMCs). Part of the myogenic component of regulation is due to interstitial cells of Cajal (ICC) that have
critical functions in gastrointestinal (GI) motility. ICC form gap junctions with SMCs and convey regulatory inputs
to a syncytium of SMCs and PDGFRa+ cells (SIP syncytium). Some ICC generate pacemaker activity that is
responsible for phasic contractions in some regions of the GI tract. ICC are closely associated with motor
neurons, express receptors for major neurotransmitters and transduce inputs from enteric motor neuro-
transmission. The physiology of ICC is important because multiple studies have suggested that defects in ICC
develop in patients and may be responsible for a range of motility disorders. While much has been learned
about ICC in other organs of the GI tract, far less is known about ICC in the colon. During the past funding period
we characterized the basic behaviors of 3 of the 4 types of colonic ICC. Little is known about ICC in the myenteric
region (ICC-MY) that do not act as conventional pacemakers, yet we hypothesize they drive major propulsive
contractions in the colon. This hypothesis will be addressed by pursuing three specific aims: 1. Determine
mechanisms responsible for propagated Ca2+ waves in ICC-MY. 2. Determine the role of ICC in generating
patterned and propulsive contractions in the colon. 3. Characterize mechanisms of action of major
neurotransmitters on activation of ICC-MY. To pursue these aims we will use imaging, optogenetic,
transgenic, electrophysiological and contractile techniques that allow in depth testing of cellular mechanisms in
ICC without disruption of their anatomical and functional interactions with other cells in colonic muscles.
Integration of ICC behaviors with SMCs and PDGFRa+ cells will also be investigated to learn how subcellular
Ca2+ signaling in ICC can generate whole organ motility patterns. The impact of enteric motor neural inputs on
Ca2+ handling mechanisms in ICC-MY will also be investigated to understand previously overlooked mechanisms
of neural regulation of colonic motility. Parallel studies will be conducted on human colonic muscles to test the
role of signature ICC conductances and Ca2+ handling mechanisms in colonic motor activity. These comparative
studies will help develop a generalized concept of ICC functions in colonic motility and determine the validity of
using mice to help clarify the functions of ICC in human motility. This project will determine the role of ICC-MY
in patterned and propulsive contractions in the colon, and studies of animals with defects in ICC will demonstrate
how/why motility is negatively impacted by defects in or loss of ICC.

## Key facts

- **NIH application ID:** 10803076
- **Project number:** 2R01DK120759-05A1
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Sal Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $591,987
- **Award type:** 2
- **Project period:** 2019-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803076

## Citation

> US National Institutes of Health, RePORTER application 10803076, Role of interstitial cells of Cajal in patterned colonic motor activity (2R01DK120759-05A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10803076. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*