Role of TRPM4 ion channel in pediatric arrhythmic syndromes

doi:10.5409/wjcp.v15.i2.114189

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Jun 9, 2026 (publication date) through May 16, 2026

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World Journal of Clinical Pediatrics

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2219-2808

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Clin Pediatr. Jun 9, 2026; 15(2): 114189
Published online Jun 9, 2026. doi: 10.5409/wjcp.v15.i2.114189

Role of TRPM4 ion channel in pediatric arrhythmic syndromes

Olesya V Melnik, Olga E Kulichik, Anastasiya K Zaytseva, Olga A Kofeynikova, Svetlana G Fetisova, Svetlana I Tarnovskaya, Yuliya V Fomicheva, Elena S Vasichkina, Boris S Zhorov, Olga V Kalinina, Anna A Kostareva

Olesya V Melnik, Yuliya V Fomicheva, Boris S Zhorov, Institute of Molecular Biology and Genetics, Almazov National Medical Research Centre, Saint Petersburg 197341, Sankt-Peterburg, Russia

Olesya V Melnik, Molecular Medicine and Cellular Biology, Institution of Medical Education, Almazov National Medical Research Centre, Saint Petersburg 197341, Sankt-Peterburg, Russia

Olga E Kulichik, ITMO University, Saint Petersburg 197101, Sankt-Peterburg, Russia

Anastasiya K Zaytseva, Svetlana I Tarnovskaya, Boris S Zhorov, Sechenov Institute of Evolutionary Physiology & Biochemistry, Saint Petersburg 194223, Sankt-Peterburg, Russia

Olga A Kofeynikova, Elena S Vasichkina, Institute of Perinatology and Pediatrics, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia

Svetlana G Fetisova, Department of Pediatric Cardiology, Institute of Perinatology and Pediatrics, Almazov National Medical Research Centre, Saint Petersburg 197341, Russia

Boris S Zhorov, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton L8S 4L8 Ontario, Canada

Olga V Kalinina, Institute of Molecular Biology and Genetics, Department of Laboratory Medicine with Clinic, Department of Molecular Medicine and Cellular Biology, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia

Anna A Kostareva, Institute of Molecular Biology and Genetics, Department of Molecular Medicine and Cellular Biology, Institution of Medical Education, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia

Author contributions: Melnik OV analyzed and interpreted the data, drafted the initial manuscript; Kulichik OE, Zaytseva AK, Tarnovskaya SI, Fomicheva YV, and Zhorov BS performed data acquisition, analyzed and interpreted the data, drafted the initial manuscript; Kofeynikova OA, Fetisova SG, and Vasichkina ES contributed to the data collection, process and clinical advice, provided the input in writing the pape; Kalinina OV and Kostareva AA analyzed and interpreted the data, designed the outline and coordinated the writing of the paper; All authors contributed to manuscript editing and approved final version of the manuscript.

Supported by the Russian Science Foundation, No. 25-15-00552.

Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript

Corresponding author: Anna A Kostareva, MD, Director, Professor, Institute of Molecular Biology and Genetics, Department of Molecular Medicine and Cellular Biology, Institution of Medical Education, Almazov National Medical Research Centre, Akkuratova Street, 2, Saint-Petersburg 197341, Russia. anna.kostareva@ki.se

Received: September 15, 2025
Revised: October 31, 2025
Accepted: January 27, 2026
Published online: June 9, 2026
Processing time: 242 Days and 13.3 Hours

Abstract

TRPM4 is a member of transient receptor potential (TRP) ion channel group which greatly contributes to cardiomyocyte function and physiology. It controls the dynamic stabilization of calcium level and is involved in sinus node regulation and cardiac conduction. Most of pathogenic variants in TRPM4 gene are associated with conduction disorders and various types of arrhythmic syndromes presenting in children and early adolescents. In addition, TRPM4 gain- and loss-of-function variants are discussed in connection to Brugada syndrome and long QT-syndrome. In this review we summarize current knowledge on the role of TRPM4 variants in pediatric arrhythmic syndromes, discuss molecular mechanisms of TRPM4 dysfunction, provide clinical illustrations and case presentations underlining the role of TRPM4 in molecular pathogenesis of arrhythmic syndromes presented in young age.

Keywords: Transient receptor potential channels; Children; Pathophysiology; Arrhythmia; Cardiac conduction

Core Tip: TRPM4 ion channel plays a crucial role in cardiovascular system and myocardial physiology. Mutations in TRPM4 are linked to cardiac conduction disorders and arrhythmic syndromes in children. Current knowledge on the role of TRPM4 variants in pediatric arrhythmic syndromes are summarized along with a discussion of molecular mechanisms of this ion channel dysfunction. Clinical illustrations underscoring the role of TRPM4 in arrhythmic syndromes manifested in childhood are presented.