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March 26, 2021International Journal of Molecular SciencesOpen Access

Deletion of Trpm4 in murine cardiac myocytes reduced peak Na+ currents, increased sensitivity to mexiletine, and slowed intraventricular conduction.

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Why the study?

Pathogenic TRPM4 variants are linked to inherited cardiac diseases, but the cardiac electrophysiological phenotypes in Trpm4 knockdown mouse models remain incompletely characterized.

Population

Isolated atrial and ventricular cardiac myocytes and explanted or in vivo mouse hearts

Comparison

Trpm4 deletion vs control

Design

Preclinical laboratory and electrophysiological study

Key result

Deletion of Trpm4 in murine cardiac myocytes reduced peak Na+ currents, increased sensitivity to mexiletine, and slowed intraventricular conduction.

Authors

LOLijo Cherian OzhathilJRJean‐Sébastien RougierPAPrakash Arullampalam

Discussion

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Member takes

Overview

TRPM4 variants merit inclusion in arrhythmia genetic panels; leaves open therapeutic targeting of channel trafficking.

Structured PICO

P
Population
Trpm4 knockout (Trpm4-/-) mice and isolated atrial and ventricular cardiac myocytes
E
Exposure
Deletion of Trpm4 gene
C
Comparator
Wild-type mice/myocytes (implied)
O
Outcome
Cardiac electrical activity (peak Na+ currents, intraventricular conduction, sensitivity to mexiletine)surrogate

TRPM4 expression regulates Nav1.5 function in murine cardiac myocytes, with its deletion reducing peak Na+ currents and slowing intraventricular conduction.

Cite This Study

Ozhathil et al. (2021) studied Trpm4 deletion. Trpm4 deletion was evaluated on Peak Na+ currents and intraventricular conduction. Deletion of Trpm4 in murine cardiac myocytes reduced peak Na+ currents, increased sensitivity to mexiletine, and slowed intraventricular conduction.

synapsesocial.com/papers/6a6c08db109fb9aed02454d5https://doi.org/10.3390/ijms22073401
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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 <i>Trpm4</i> alters the function and expression of Na <sub>V</sub> 1.5 channel in murine cardiac myocytes2020
  2. 2Knockdown of the TRPM4 channel alters cardiac electrophysiology and hemodynamics in a sex- and age-dependent manner in mice2022
  3. 3Glycosylation of the murine cardiac channel TRPM4 is altered by the pathogenic p.I376T variant.2026
  4. 4Four TRPM4 Cation Channel Mutations Found in Cardiac Conduction Diseases Lead to Altered Protein Stability2018 · 50 citations
  5. 5Timing of Myocardial <i>Trpm7</i> Deletion During Cardiogenesis Variably Disrupts Adult Ventricular Function, Conduction, and Repolarization2013 · 107 citations