# Pacemaker cells and mechanism in the renal pelvis

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 2022 · $477,730

## Abstract

Project Summary
The renal pelvis (RP), a smooth muscle organ that transports urine from the kidney to the ureter, generates
regular rhythmic contractions that are vital for urine transport and bladder filling. Propagating contractions
originate in the most proximal region of the RP, where specialized cells, called “atypical” smooth muscle cells
(ASMCs)”, have been proposed to serve as the pacemaker cells. However, identification of ASMCs has been
imprecise, and thus experimental findings regarding their phenotype and functions are controversial. Ambiguities
arise from the lack of specific markers for ASMCs and have prevented understanding the role of ASMC in driving
peristaltic contractions or the mechanism of pacemaker activity in the RP. Newer technologies can now identify
specific cell-types within tissues composed of heterogeneous populations of cells. This study will employ strains
of mice with cell-specific reporters and optogenetic sensors to clarify how the pacemaker and responder cells of
the RP generate peristaltic contractions. Our preliminary data show that the specialized cells, ASMCs, express
platelet-derived-growth-factor-receptor-alpha (PDGFRα), and using transgenic mice that express a histone 2B-
eGFP fusion protein driven off the endogenous PDGFRα+ promoter, we can identify these cells unequivocally in
intact tissues or in enzymatic dispersions of the tissues. We hypothesize that PDGFRα+ cells are pacemaker
cells in the renal pelvis. The following Specific Aims will be addressed: 1. Test the hypothesis that PDGFRα+
are the primary pacemaker cells of the RP; 2. Investigate the dynamics of Ca2+ signaling in PDGFRα+ cells; 3.
Elucidate the specific mechanisms of pacemaker generation and propagation. Because of their specialized
function as pacemaker cells, PDGFRα+ cells are likely to have specialized gene expression patterns that encode
essential ionic conductances and other signaling molecules to facilitate pacemaker activity. This will be
investigated by analysis of gene expression in FACS-enriched populations PDGFRα+ cells isolated from the
proximal RP of the reporter strain of mice. Mice expressing a genetically encoded Ca2+ indicator (GECI) in
PDGFRα + cells will be used to image Ca2+ signaling in PDGFRα+cells in situ. The ion channels activated by Ca2+
dynamics will be determined and the consequences of this conductance in RP peristalsis will be evaluated.
Preliminary data show that PDGFRα+ cells exhibit dynamic Ca2+ signaling in situ and express the Ca2+-activated-
Cl- channel, Ano1, making this a prime candidate for the pacemaker conductance. This project will serve as a
basis for future studies to understand developmental or pathological problems affecting RP function.
OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10397176
- **Project number:** 5R01DK124509-03
- **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:** $477,730
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397176

## Citation

> US National Institutes of Health, RePORTER application 10397176, Pacemaker cells and mechanism in the renal pelvis (5R01DK124509-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10397176. Licensed CC0.

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