# Diversity Supplement - Regulation of cardiac pacemaker cell cyotarchitecture

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $38,318

## Abstract

Abstract:
Rhythmic beating of the heart is controlled by electrical impulses initiated by sinoatrial (SA) node pacemaker cells
(PCs). SA node dysfunction manifests across a broad range of human cardiac disease and is currently the leading
cause for the surgical implantation of mechanical pacing devices. Regardless etiology or age of presentation, the
cellular defects that trigger SA node dysfunction are poorly understood, highlighting the urgent need to define the
cellular, molecular, and microenvironmental interactions that support and sustain PCs electrical activity. Of
significant interest to this proposal, PCs have the unique capacity to rhythmically initiate electrical impulse under
ionic conditions that should theoretically suppress their activity. It is becoming increasingly apparent that specific
cytoarchitectural features including the lack of high-conductance intercalated disks and small cell size, confer
electrogenic characteristics that protect PCs from ionic suppression. Dysregulation of PC cytoarchitecture,
therefore, represents a significant vulnerability to electrical dysfunction and cardiac arrhythmia. Currently, almost
nothing is known regarding the regulation and/or maintenance of PC cytoarchitecture. The long-term objectives of
this proposal are to address this fundamental gap in current knowledge by defining the developmental events that
initially pattern the phenotypic features required for PC function. Our overall working hypothesis is that unique
microenvironmental conditions present within the forming SA node suppress adherens junction formation which, in
turn, promotes the cellular attributes that support PC excitability (i.e. small size and poor electrical coupling). This
hypothesis will be tested in three specific aims that will define whether the SA node microenvironment controls
cytoarchitecture (Aim 1), establish whether loss of adherens junction formation regulates PC size/electrical activity
(Aim 2), and identify the upstream molecular regulators of the PC phenotype (Aim 3). By defining the events that
pattern PC cytoarchitecture this proposal will create a new comprehensive and mechanistic model of PC
development. Furthermore, by defining the conditions that pattern and maintain PC phenotype, these studies will
uncover pathways that may become disrupted in juvenile and/or adult cases of SA node dysfunction, as well as
establish basic cell biological paradigms that will need to be accounted for as cellular-based therapeutics for the
correction of cardiac arrhythmias continue to advance.

## Key facts

- **NIH application ID:** 10154829
- **Project number:** 3R01HL146626-02S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Michael C Bressan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,318
- **Award type:** 3
- **Project period:** 2019-04-05 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154829

## Citation

> US National Institutes of Health, RePORTER application 10154829, Diversity Supplement - Regulation of cardiac pacemaker cell cyotarchitecture (3R01HL146626-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10154829. Licensed CC0.

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