ArticlePloS one2014
Trpm4 gene invalidation leads to cardiac hypertrophy and electrophysiological alterations.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- Glycosylation of the murine cardiac channel TRPM4 is altered by the pathogenic p.I376T variant.Experimental physiology · 2026Article
- Comprehensive bioinformatic analysis reveals TRPM4 as a biomarker for pan-cancer progression and macrophage infiltration.Discover oncology · 2026Article
- The TRP channels serving as chemical-to-electrical signal converter.Physiological reviews · 2025Review
- Diverse activity of miR-150 in Tumor development: shedding light on the potential mechanisms.Cancer cell international · 2023Review
- Uncoupling cytosolic calcium from membrane voltage by transient receptor potential melastatin 4 channel (TRPM4) modulation: A novel strategy to treat ventricular arrhythmias.Heart rhythm O2 · 2023Review
- The Role of TRPM4 in Cardiac Electrophysiology and Arrhythmogenesis.International journal of molecular sciences · 2023Review
- Review
- Ion Channels in the Development and Remodeling of the Aortic Valve.International journal of molecular sciences · 2023Review
- Article
- Isoform changes of action potential regulators in the ventricles of arrhythmogenic phospholamban-R14del humanized mouse hearts.Metabolism: clinical and experimental · 2023Article
- Article
- Differential effects of TRPM4 channel inhibitors on Guinea pig urinary bladder smooth muscle excitability and contractility: Novel 4-chloro-2-[2-(2-chloro-phenoxy)-acetylamino]-benzoic acid (CBA) versus classical 9-phenanthrol.Pharmacology research & perspectives · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- The Role ofGenes · 2022Article
- A Central Role for TRPM4 in CaInternational journal of molecular sciences · 2022Article
- Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel-Part 1: Modulation of TRPM4.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The novel TRPM4 c.448G>T variant is associated with familial conduction disorders, cardiomyopathy, and sudden cardiac death.Cardiology journal · 2022Article
- Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel-Part 2: TRPM4 in Health and Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Electrophysiological Effects of the Transient Receptor Potential Melastatin 4 Channel Inhibitor (4-Chloro-2-(2-chlorophenoxy)acetamido) Benzoic Acid (CBA) in Canine Left Ventricular Cardiomyocytes.International journal of molecular sciences · 2021Article
- Mapping the expression of transient receptor potential channels across murine placental development.Cellular and molecular life sciences : CMLS · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleTRPM4 is a non-selective Ca2+-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear.
objectivesWe aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4-/-) model. METHODS AND
resultsMorpho-functional analysis revealed left ventricular (LV) eccentric hypertrophy in Trpm4-/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks) when compared to Trpm4+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4-/- mice were smaller than Trpm4+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4-/-neonatal stage, suggesting hyperplasia. Adult Trpm4-/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4-/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca2+ or K+ currents involved in the repolarizing phase.
conclusionsTRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular electrical activity which impact heart development.
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