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October 27, 2022Open Access

In adult male mice, Trpm4 knockdown significantly reduced heart rate and increased heart rate variability, while the TRPM4 inhibitor NBA triggered third-degree atrioventricular block in 40% of wild-type hearts.

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Why the study?

Clinical studies have linked TRPM4 mutations to cardiac disorders, but its exact roles in the heart remain unclear.

Does Trpm4 knockdown alter cardiac electrophysiology and hemodynamics in mice?

Population

Male and female Trpm4 knockdown and wild-type mice aged 5- to 12-weeks-old or 24-week-old or more

Comparison

Trpm4 knockdown (Trpm4 -/-) mice vs wild-type mice

Design

Preclinical animal study

Key result

In adult male mice, Trpm4 knockdown significantly reduced heart rate and increased heart rate variability, while the TRPM4 inhibitor NBA triggered third-degree atrioventricular block in 40% of wild-type hearts.

Authors

PAPrakash ArullampalamMEMaria C. EssersJRJean‐Sébastien Rougier

Discussion

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Member takes

Overview

May identify TRPM4 as therapeutic target in conduction disorders; animal data leave clinical translation open.

Structured PICO

Does Trpm4 knockdown alter cardiac electrophysiology and hemodynamics in mice?

P
Population
Male and female Trpm4 knockdown and wild-type mice aged 5-12 weeks or ≥24 weeks were used to investigate the role of TRPM4 in cardiac physiology.
I
Intervention
Trpm4 knockdown (genetic model) and application of 5 µM NBA
C
Comparator
Wild-type mice
O
Outcome
Cardiac electrophysiology and hemodynamics assessed via surface ECG, echocardiography, pseudo and intracardiac ECGs, western blots, and mRNA quantificationssurrogate

TRPM4 plays a crucial role in cardiac structure and electrical function, with its knockdown inducing sex- and age-dependent alterations in heart rate and ventricular function in mice.

Limitations

  • Discrepancies with previous Trpm4 -/- models potentially due to different genetic backgrounds or substrains.
  • Right ventricular systolic function assessment was indirect via pulmonary artery scanning due to technical challenges with echocardiography.

Cite This Study

Arullampalam et al. (2022) studied Cardiac electrophysiology and hemodynamics. Trpm4 knockdown and NBA inhibitor vs. Wild-type mice and vehicle was evaluated on Cardiac electrophysiology and hemodynamics (heart rate, heart rate variability, and atrioventricular conduction). In adult male mice, Trpm4 knockdown significantly reduced heart rate and increased heart rate variability, while the TRPM4 inhibitor NBA triggered third-degree atrioventricular block in 40% of wild-type hearts.

synapsesocial.com/papers/6a6c08db109fb9aed02454cdhttps://doi.org/10.1101/2022.10.26.513825
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Deletion of Trpm4 Alters the Function of the Nav1.5 Channel in Murine Cardiac Myocytes2021 · 25 citations
  2. 2Deletion of <i>Trpm4</i> alters the function and expression of Na <sub>V</sub> 1.5 channel in murine cardiac myocytes2020
  3. 3Glycosylation of the murine cardiac channel TRPM4 is altered by the pathogenic p.I376T variant.2026
  4. 4The TRPM4 mutation p.I377T is a direct cause of electrophysiological alterations and increases arrhythmia sensitivity in mouse cardiac muscle2026
  5. 5Timing of Myocardial <i>Trpm7</i> Deletion During Cardiogenesis Variably Disrupts Adult Ventricular Function, Conduction, and Repolarization2013 · 107 citations