# Chemo-mechanical signaling in atrial myocytes

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $661,690

## Abstract

Atrial myocyte cell biology will be examined in isolated single cells in vitro and mice in vivo to
characterize quantitatively how chemo-mechanical signaling works in health and disease. This signaling
pathway is activated by changes in myocyte shape as happens when the atria fill with blood, and myocytes
stretch, during diastolic filling. Using extremely high temporal and spatial resolution imaging the PIs will
examine how chemo-mechanical signaling contributes to subcellular changes in Ca2+, excitation-contraction
coupling to influence both electrical and Ca2+ instability. Preliminary results suggest that newly identified large
axial tubules in atrial myocytes (discovered by the PIs) along with Ca2+ release "super-hubs" play a role in a
unique Ca2+ signaling system found in atrial myocytes. Furthermore, the mechano-chemo X-ROS pathway
discovered by the PIs in ventricular myocytes is likely to have a special role to play in atrial myocytes. This
signaling pathway links the mechanics of cellular stretch, transmitted through microtubules, to the generation of
local subcellular reactive oxygen species (ROS) that likely target multiple Ca2+ signaling proteins such as
CaMKII and RyR2. Preliminary results suggest this X-ROS signaling is very active in atrial myocytes and may
be linked to the novel structures described by the PIs. The proposed work will identify quantitatively the
contributions of the special structures, X-ROS signaling and chemo-mechanical signaling to the normal
physiology of atrial myocytes and the contributions to the development of atrial fibrillation (AF). Two very
different mouse models of AF will be used along with specific transgenic mice to quantitatively characterize
Ca2+ signaling and cellular electrophysiology in atrial myocytes and determine how chemo-mechanical
signaling contributes to cellular physiology and pathophysiology. This investigation will provide critically
important new information on how atrial myocytes work and fail in health and disease. The likely new
discoveries produced by the proposed work will broaden our understanding of atrial cell biology and lay the
foundation for innovative, effective and novel therapies for atrial dysfunction and AF.

## Key facts

- **NIH application ID:** 9849799
- **Project number:** 5R01HL142290-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** William Jonathan Lederer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $661,690
- **Award type:** 5
- **Project period:** 2019-01-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849799

## Citation

> US National Institutes of Health, RePORTER application 9849799, Chemo-mechanical signaling in atrial myocytes (5R01HL142290-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9849799. Licensed CC0.

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