What is the clinical evidence from this study?

Study design: Other. Population: TRPM4 p.I376T variant. Intervention: TRPM4 p.I376T variant vs. Wild-type. Primary outcome: Cardiac electrophysiology (surface ECGs), TRPM4 protein surface expression, and TRPM4 current.

What does this research mean for the field?

The TRPM4 p.I376T variant decreases the amount of highly glycosylated TRPM4 protein expressed in the murine heart without altering electrical activity at young ages. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine the cardiac physiological and electrophysiological consequences of the progressive heart block-associated TRPM4 p.I376T variant using a novel knock-in mouse model.

May 1, 2026

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 amount of highly glycosylated TRPM4 protein expressed.

Population

Murine cardiomyocytes and hearts

Comparison

TRPM4 p.I376T variant vs wild-type cardiomyocytes

Authors

SGSabrina GuichardUniversity of Bern ELEmanuele di LorenzoUniversity of Bern DSDominic SchneiterUniversity of Bern

Discussion

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Implication

No impact on young patient arrhythmia management; leaves open glycosylation's role in TRPM4-related cardiac phenotypes.

Key Points

To determine the cardiac physiological and electrophysiological consequences of the progressive heart block-associated TRPM4 p.I376T variant using a novel knock-in mouse model.
Phenotyped male and female homozygous Trpm4 knock-in (Trpm4 I376T/I376T) and wild-type mice across four young age groups (12, 18, 24, and 36 weeks old) via surface electrocardiography.
Quantified cardiac TRPM4 protein surface expression and post-translational modification using Western blot analysis.
Measured TRPM4 currents in freshly isolated ventricular cardiomyocytes from both genotypes using patch-clamp electrophysiology.
Surface electrocardiogram recordings demonstrated no statistically significant differences in cardiac electrophysiology between Trpm4 I376T/I376T and wild-type mice at 12, 18, 24, or 36 weeks of age.
Western blot analysis showed a significant reduction in the highly glycosylated fraction of the TRPM4 protein in Trpm4 I376T/I376T cardiac tissue compared to wild-type tissue.
Patch-clamp experiments revealed no significant differences in TRPM4 current amplitudes between isolated Trpm4 I376T/I376T and wild-type ventricular cardiomyocytes.

Structured PICO

Population

Male and female Trpm4 knock-in and wild-type mice aged 12 to 36 weeks evaluated for cardiac electrophysiology and protein expression.

Exposure

Trpm4 p.I376T variant (knock-in model)

Comparator

Wild-type mice

Outcome

Cardiac electrophysiology (surface ECGs), TRPM4 protein surface expression, and TRPM4 currentsurrogate

The pathogenic TRPM4 p.I376T variant alters channel glycosylation in a murine model but does not affect baseline cardiac electrical activity at young ages.

Cite This Study

Guichard et al. (2026) studied TRPM4 p.I376T variant. TRPM4 p.I376T variant vs. Wild-type 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 amount of highly glycosylated TRPM4 protein expressed.

synapsesocial.com/papers/69f443cb967e944ac5566dd0 https://doi.org/10.1113/ep093873

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

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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