ArticleThe Journal of clinical investigation2009
Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 317 citations in OpenAlex.
- Meta-Analysis of Mechano-Sensitive Ion Channels in Human Hearts: Chamber- and Disease-Preferential mRNA Expression.International journal of molecular sciences · 2023Pooled it
- A Postzygotic TRPM4 Variant in a Patient with Inflammatory Linear Verrucous Epidermal Nevus.Acta dermato-venereologica · 2026Article
- Glycosylation of the murine cardiac channel TRPM4 is altered by the pathogenic p.I376T variant.Experimental physiology · 2026Article
- Temperature-dependent ligand relocation reveals plasticity of TRPM4 inhibition.bioRxiv : the preprint server for biology · 2026Article
- Role of TRPM4 ion channel in pediatric arrhythmic syndromes.World journal of clinical pediatrics · 2026Review
- Heat- and PIP2-dependent TRPM4 activity underlies mutually exclusive human diseases.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural biology of the TRPM4 channel: architecture, modulation, and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Structural landscape of activation, desensitization and inhibition in the human TRPM4 channel.Nature structural & molecular biology · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Multigenerational TRPM4 variant presenting with fetal atrioventricular block and atrial arrhythmias.HeartRhythm case reports · 2025Article
- The TRP channels serving as chemical-to-electrical signal converter.Physiological reviews · 2025Review
- Late outcomes of congenital and childhood non-immune, isolated atrioventricular block: a French nationwide retrospective cohort study.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- SUMO Regulation of Ion Channels in Health and Disease.Physiology (Bethesda, Md.) · 2025Review
- Identification and development of TRPM4 antagonists to counteract neuronal excitotoxicity.iScience · 2024Article
- Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.Expert opinion on therapeutic targets · 2024Review
- Sodium-Permeable Ion Channels TRPM4 and TRPM5 are Functional in Human Gastric Parietal Cells in Culture and Modulate the Cellular Response to Bitter-Tasting Food Constituents.Journal of agricultural and food chemistry · 2024Article
- TRPM channels in health and disease.Nature reviews. Nephrology · 2024Review
- Sudden death in epilepsy: the overlap between cardiac and neurological factors.Brain communications · 2024Review
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
- Cholinergic stimulation stabilizes TRPM4 in the plasma membrane of cortical pyramidal neurons.Frontiers in cell and developmental biology · 2024Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progressive familial heart block type I (PFHBI) is a progressive cardiac bundle branch disease in the His-Purkinje system that exhibits autosomal-dominant inheritance. In 3 branches of a large South African Afrikaner pedigree with an autosomal-dominant form of PFHBI, we identified the mutation c.19G-->A in the transient receptor potential cation channel, subfamily M, member 4 gene (TRPM4) at chromosomal locus 19q13.3. This mutation predicted the amino acid substitution p.E7K in the TRPM4 amino terminus. TRPM4 encodes a Ca2+-activated nonselective cation (CAN) channel that belongs to the transient receptor potential melastatin ion channel family. Quantitative analysis of TRPM4 mRNA content in human cardiac tissue showed the highest expression level in Purkinje fibers. Cellular expression studies showed that the c.19G-->A missense mutation attenuated deSUMOylation of the TRPM4 channel. The resulting constitutive SUMOylation of the mutant TRPM4 channel impaired endocytosis and led to elevated TRPM4 channel density at the cell surface. Our data therefore revealed a gain-of-function mechanism underlying this type of familial heart block.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.