# Inhibitory mechanisms of PDGFRa+ interstitial cells in gastrointestinal motility

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $444,558

## Abstract

Summary
Normal motor activity in the gastrointestinal (GI) tract relies upon coordinated contractions of the smooth muscle
cells (SMCs) that line its walls. The ultimate contractile behavior of GI muscles depends upon the state of SMC
excitability when regulatory inputs (e.g. nerve reflexes, hormones, etc) are applied. This project has developed
the concept of the SIP syncytium, an electrically coupled tissue consisting of SMCs, interstitial cells of Cajal and
PDGFRa+ cells, that establishes the basal excitability of smooth muscles, organizes contractile behavior into
phasic contractions, and transduces signals from a variety of motor neurons. GI motility in fact results from the
integrated output of the SIP syncytium. During the past funding period we discovered that PDGFRa+ cells are a
novel class of regulatory cells and essential component of the SIP syncytium. These cells express receptors
and ion channels consistent with mediation of purinergic inhibitory regulation in the GI tract. Through isolation
and purification of PDGFRa+ cells by FACS we performed deep sequencing to better understand the phenotypes
of these cells. The expression data suggest that many additional pathways, such as adrenergic and inhibitory
neuropeptides, contribute to the regulatory functions of PDGFRa+ cells. The focus of the upcoming funding
period is to test the hypothesis that sympathetic nerve and enteric inhibitory neuropeptide signals are also
transduced by PDGFRa+ cells, making these cells a convergent central integrator of inhibitory regulation of
colonic motility. We will first clarify the tissue level responses mediated by sympathetic neurotransmission and
inhibitory neuropeptides that can be attributed to mechanisms expressed uniquely by PDGFRa+ cells.
Preliminary data clearly show direct sympathetic innervation and inhibitory effects of PDGFRa+ cells powerful
enough to halt propulsive contractions in the colon. This is an exciting new concept of how stressful conditions
might radically alter bowel habits through PDGFRa+ cells. Our findings suggest that any stimulus coupled to
Ca2+ transients in PDGFRa+ cells will activate small conductance Ca2+-activated K+ channels and initiate
powerful hyperpolarization and inhibitory influences on the SIP syncytium. We will use cutting edge Ca2+ imaging
techniques, including cell-specific optogenetic sensors, to better understand the cells and sequence of events
that occurs in peptidergic and sympathetic inhibitory responses mediated by PDGFRa+ cells. Finally, in studies
of single cells we will utilize electrophysiological and imaging techniques to expand our knowledge of ionic
conductances that might be used by PDGFRa+ cells to generate integrated inhibitory regulation. We will also
study the role of Ca2+ stores in the responses and how stores are maintained for long term and repetitive
inhibitory responses. Completion of the specific aims will provide novel information about an important cell type
never been considere...

## Key facts

- **NIH application ID:** 10480070
- **Project number:** 5R01DK091336-10
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Masaaki Kurahashi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $444,558
- **Award type:** 5
- **Project period:** 2013-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480070

## Citation

> US National Institutes of Health, RePORTER application 10480070, Inhibitory mechanisms of PDGFRa+ interstitial cells in gastrointestinal motility (5R01DK091336-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10480070. Licensed CC0.

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