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July 6, 2020Open Access

Deletion of Trpm4 in murine cardiac myocytes reduced peak Na+ currents by up to 30% and decreased NaV1.5 protein expression by 50% in ventricles, resulting in slower intraventricular conduction.

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Why the study?

Cardiac electrophysiological phenotypes in Trpm4 knockdown mouse models remained incompletely characterized despite TRPM4 variants being linked to conduction block and Brugada syndrome.

Does Trpm4 deletion alter Na+ currents and NaV1.5 expression in murine cardiac myocytes?

Population

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

Comparison

Trpm4 deletion (Trpm4 -/-) vs wild-type

Design

Preclinical experimental study using patch clamp, immunohistochemistry, and ECGs

Key result

Deletion of Trpm4 in murine cardiac myocytes reduced peak Na+ currents by up to 30% and decreased NaV1.5 protein expression by 50% in ventricles, resulting in slower intraventricular conduction.

Authors

LOLijo Cherian OzhathilJRJean‐Sébastien RougierPAPrakash Arullampalam

Discussion

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Overview

TRPM4 variants may warrant inclusion in arrhythmia genetic panels; leaves open pathogenicity and clinical utility pending validation.

Structured PICO

Does Trpm4 deletion alter Na+ currents and NaV1.5 expression in murine cardiac myocytes?

P
Population
Male Trpm4-/- mice and wildtype littermates aged 12-15 weeks were used to study the functional consequences of Trpm4 deletion on cardiac electrical activity.
E
Exposure
Deletion of Trpm4 gene
C
Comparator
Wild-type mice (implied)
O
Outcome
Cardiac electrical activity, peak Na+ currents, intraventricular conduction, and NaV1.5 protein expressionsurrogate

Trpm4 deletion reduces peak Na+ currents and NaV1.5 protein expression in murine cardiac myocytes, suggesting a novel regulatory role of Trpm4 in cardiac electrophysiology.

Limitations

  • Discrepancies with previous studies regarding baseline cardiac phenotypes
  • Did not address whether Trpm4 and NaV1.5 directly or indirectly interact at mRNA or protein level
  • Effect on heart rate in surface ECGs could be due to anesthesia

Cite This Study

Ozhathil et al. (2020) studied Cardiac electrical activity (preclinical). Trpm4 deletion vs. Wildtype (WT) littermates was evaluated on Peak Na+ current density and NaV1.5 protein expression. Deletion of Trpm4 in murine cardiac myocytes reduced peak Na+ currents by up to 30% and decreased NaV1.5 protein expression by 50% in ventricles, resulting in slower intraventricular conduction.

synapsesocial.com/papers/6a6c08db109fb9aed02454d6https://doi.org/10.1101/2020.07.06.188961
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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. 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