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May 3, 2026Open Access

Glycosylation of the murine cardiac channel TRPM4 is altered by the pathogenic p.I376T variant.

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Key result

The TRPM4 p.I376T variant did not alter electrical activity in young murine hearts but significantly decreased the highly glycosylated fraction of the TRPM4 protein.

Why the study?

The study aimed to investigate the consequence of the channel variant TRPM4 p.I376T in cardiac physiology in a newly generated knock-in mouse line.

Does the TRPM4 p.I376T variant alter cardiac electrophysiology or TRPM4 protein expression in a murine model?

Population

Male and female Trpm4 knock-in (Trpm4I376T/I376T) and wild-type mice aged 12, 18, 24, and 36 weeks

Comparison

Trpm4I376T/I376T knock-in mice vs wild-type mice

Design

Animal experimental study

Authors

SGSabrina GuichardUniversity of BernELEmanuele di LorenzoUniversity of BernDSDominic SchneiterUniversity of Bern

Discussion

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Implication

Challenges causative role of TRPM4 p.I376T in progressive heart block; leaves open contributions of modifiers or human-specific mechanisms.

Key Points

  • To investigate how the TRPM4 p.I376T variant impacts cardiac physiology in a mouse model.
  • Generated Trpm4 knock-in mouse line (Trpm4I376T/I376T) and wild-type controls.
  • Phenotyped mice using surface ECGs to assess cardiac electrophysiology.
  • Performed Western blots to analyze TRPM4 protein expression levels in cardiac tissue.
  • No significant differences in cardiac electrophysiology were found between Trpm4I376T/I376T and wild-type mice at various ages.
  • A significant decrease in highly glycosylated TRPM4 protein was observed in Trpm4I376T/I376T hearts compared to wild-type.
  • TRPM4 current in ventricular cardiomyocytes was unchanged between the two genotypes.

Structured PICO

Does the TRPM4 p.I376T variant alter cardiac electrophysiology or TRPM4 protein expression in a murine model?

P
Population
Male and female Trpm4 knock-in (Trpm4I376T/I376T) and wild-type mice at 12, 18, 24, and 36 weeks of age
I
Intervention
TRPM4 p.I376T variant (Trpm4 knock-in)
C
Comparator
Wild-type mice
O
Outcome
Cardiac electrophysiology (surface ECGs), TRPM4 protein surface expression, and TRPM4 currentsurrogate

The TRPM4 p.I376T variant reduces highly glycosylated TRPM4 protein expression in the murine heart but does not alter baseline electrical activity at young ages.

Cite This Study

Guichard et al. (2026) studied Progressive heart block type I (TRPM4 p.I376T variant). Trpm4 knock-in (Trpm4I376T/I376T) vs. Wild-type mice was evaluated on Cardiac electrophysiology (surface ECGs), TRPM4 protein surface expression, and TRPM4 current. The TRPM4 p.I376T variant did not alter electrical activity in young murine hearts but significantly decreased the highly glycosylated fraction of the TRPM4 protein.

synapsesocial.com/papers/69f6e5cf8071d4f1bdfc664fhttps://doi.org/10.48620/97353
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Also Consider

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

  1. 1Glycosylation of the murine cardiac channel TRPM4 is altered by the pathogenic p.I376T variant2026
  2. 2The TRPM4 mutation p.I377T is a direct cause of electrophysiological alterations and increases arrhythmia sensitivity in mouse cardiac muscle2026
  3. 3Deletion of Trpm4 Alters the Function of the Nav1.5 Channel in Murine Cardiac Myocytes2021 · 25 citations
  4. 4Four TRPM4 Cation Channel Mutations Found in Cardiac Conduction Diseases Lead to Altered Protein Stability2018 · 52 citations
  5. 5Deletion of Trpm4 alters the function and expression of Na V 1.5 channel in murine cardiac myocytes2020