# TRPV4 and Calcium Dependent Ventricular Arrhythmia Following Ischemia-Reperfusion

> **NIH NIH F31** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $2,068

## Abstract

Project Summary/Abstract:
Ventricular Arrhythmia is a leading cause of death following Myocardial Infarction (MI), with high incidence
among aging populations. Recent data from our laboratory show that the osmotically activated Transient
Receptor Potential Vanilloid 4 (TRPV4) cation channel increases expression in ventricular cardiomyocytes with
advancing age. Ischemia-Reperfusion (I/R) is associated with both Ca2+ overload and hypoosmotic stress on the
myocardium. Ca2+ overload disturbs excitation-contraction coupling and promotes arrhythmia by increasing
diastolic Ca2+ release and membrane depolarization. Thus, this proposal tests the hypothesis that hypoosmotic
stress during I/R activates TRPV4-mediated Ca2+ influx, which contributes to Ca2+ overload and
arrhythmogenesis. Specific Aim 1 is to investigate the role of TRPV4 in isolated cardiomyocyte Ca2+ influx,
membrane potential, and Ca2+ homeostasis following hypoosmotic stress. Patch clamp recording of membrane
potential and membrane Ca2+ currents will be measured in cardiomyocytes from Aged mice (24-26 month, with
high TRPV4 expression), Young mice (3-6 month, with low TRPV4 expression), and Young mice with inducible
transgenic cardiac-specific TRPV4 overexpression (Young TRPV4 Overexpressors). Isolated cardiomyocytes
from the same groups, but with an additional GCaMP6f Ca2+ sensor transgene𝜇𝜇will also be subjected to
hypoosmotic stress and intracellular Ca2+ homeostasis will be assessed using laser scanning confocal
microscopy in the presence and absence of TRPV4 antagonism (HC067047, 1 M). Specific Aim 2 is to
investigate the arrhythmogenic role of TRPV4 in Langendorff-perfused isolated hearts subjected to I/R.
Reversible ligation of the left anterior descending artery (LAD) will induce I/R in Aged, Young, and Young TRPV4
Overexpressor hearts. Sharp microelectrode recordings of cardiomyocytes from LAD-supplied myocardium will
be taken prior to, during, and following I/R in the presence and absence of TRPV4 antagonism. The same
protocol will be conducted on Langendorff perfused Young and Young TRPV4 Overexpressor isolated hearts
(with the GCaMP6f Ca2+ sensor) while imaging of the left-ventricular free wall by laser scanning confocal
microscopy. This in situ imaging will allow for measurement of arrhythmogenic diastolic Ca2+ release events in
the intact heart during I/R. This project investigates a novel therapeutic target for preventing Ca2+-dependent
ventricular arrhythmias following myocardial infarction in aging populations. Additionally, the proposal provides
valuable training to the applicant in conducting cardiovascular research.

## Key facts

- **NIH application ID:** 9922120
- **Project number:** 5F31HL147559-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Deborah Peana
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,068
- **Award type:** 5
- **Project period:** 2019-05-01 → 2020-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922120

## Citation

> US National Institutes of Health, RePORTER application 9922120, TRPV4 and Calcium Dependent Ventricular Arrhythmia Following Ischemia-Reperfusion (5F31HL147559-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9922120. Licensed CC0.

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