Article
Multidisciplinary Sciences
See Wee Low, Yahui Gao, Shunhui Wei, Bo Chen, Bernd Nilius, Ping Liao
Summary: TRPM4 is a calcium-activated non-selective monovalent cation channel involved in diseases such as stroke. Monoclonal antibodies M4M and M4M1 were developed to target human TRPM4, with M4M showing higher efficacy in blocking the channel. These antibodies have the potential for therapeutic application in conditions involving TRPM4 dysfunction.
SCIENTIFIC REPORTS
(2021)
Review
Neurosciences
Andy Pironet, Frone Vandewiele, Rudi Vennekens
Summary: Cardiac arrhythmias pose a significant health threat, but are difficult to predict, prevent, and treat. Disturbed Ca2+ homeostasis in cardiac muscle cells has been identified as a key mechanism in the occurrence of arrhythmias. TRPM4, a Ca2+-activated channel, has been linked to Ca2+-induced arrhythmias, contributing to membrane depolarisation and increased excitability. Evidence from genetically modified mice, human patient mutations, and a TRPM4 blocking compound support this hypothesis. This overview provides insights into our understanding of Ca2+-dependent arrhythmias.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Multidisciplinary Sciences
Evan Yamasaki, Sher Ali, Alfredo Sanchez Solano, Pratish Thakore, Megan Smith, Xiaowei Wang, Cassandre Labelle-Dumais, Douglas B. Gould, Scott Earley
Summary: Gould syndrome is a rare multisystem disorder caused by autosomal dominant mutations in the COL4A1 and COL4A2 genes. The age-related cerebral vascular dysfunction in Col4a1+/G394V mice is due to the loss of depolarizing TRPM4 currents caused by PIP2 depletion, revealing an age-dependent mechanism of cerebral small vessel diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Paulina Stoklosa, Anna Borgstroem, Barbara Hauert, Roland Baur, Christine Peinelt
Summary: This study validated novel TRPM4 inhibitors in CRC cells, demonstrating their potential anti-cancer effects. NBA showed promising inhibition on proliferation and viability in CRC cells, highlighting its candidacy as a new TRPM4 inhibitor for further studies in cancer models and other diseases.
Article
Developmental Biology
Alexandre Fouchet, Harlyne Mpweme Bangando, Margaux Aize, Christophe Simard, Romain Guinamard
Summary: Inappropriate uterine contractions during pregnancy or menses are a concern. The TRPM4 ion channel has been identified as a potential pharmacological target for better control of myometrial activity in mice.
Article
Pharmacology & Pharmacy
Prakash Arullampalam, Barbara Preti, Daniela Ross-Kaschitza, Martin Lochner, Jean-Sebastien Rougier, Hugues Abriel
Summary: The study reveals species-dependent differences in the response of TRPM4 inhibitors on human and mouse TRPM4 channels. While CBA and NBA can effectively inhibit human TRPM4, they may have different effects on mouse TRPM4. Furthermore, the application of 9-phenanthrol may lead to opposite outcomes for mouse TRPM4 depending on the site of application.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bo Chen, Shunhui Wei, See Wee Low, Charlene Priscilla Poore, Andy Thiam-Huat Lee, Bernd Nilius, Ping Liao
Summary: Reperfusion therapy for acute ischemic stroke aims to restore blood flow but can cause reperfusion injury. Delayed recanalization increases the risk of severe injury. The TRPM4-blocking antibody M4P has been shown to alleviate reperfusion injury and improve outcomes. In this study, M4P treatment improved vascular morphology, reduced leakage, and improved cerebral perfusion, resulting in reduced infarct volume and mortality rate in a delayed stroke reperfusion rat model.
Article
Neurosciences
Keyong Li, Yingtang Shi, Elizabeth C. Gonye, Douglas A. Bayliss
Summary: The study demonstrates the involvement of TRPM4 channels in large subthreshold membrane potential oscillations underlying tonic action potential discharge in the locus coeruleus and suprachiasmatic nucleus. Blocking TRPM4 inhibits the oscillations and contributes to shaping the distinctive electroresponsive properties of these brain regions.
Article
Cell Biology
Keyong Li, Stephen B. G. Abbott, Yingtang Shi, Pierce Eggan, Elizabeth C. Gonye, Douglas A. Bayliss
Summary: The study investigates the intrinsic ionic mechanisms underlying the characteristic metronomic firing activity of RTN neurons, implicating the role of TRPM4 in supporting pacemaker-like firing. TRPM4-dependent oscillatory activity and action potential discharge are modulated by extracellular acidification and serotonin (5-HT).
Review
Biochemistry & Molecular Biology
Yaopeng Hu, Jiehui Cang, Keizo Hiraishi, Takayuki Fujita, Ryuji Inoue
Summary: The transient receptor potential melastatin 4 (TRPM4) channel is a non-selective cation channel that plays a crucial role in regulating intracellular Ca2+ homeostasis/dynamics in various cellular functions. It has a significant impact on the electrical activity of cardiomyocytes by depolarizing the membrane, and is associated with the development of cardiac arrhythmias. This review highlights the potential of targeting the TRPM4 channel as a novel therapeutic approach for preventing and treating cardiac arrhythmias.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
Jianlin Feng, Pengyu Zong, Jiajie Yan, Zhichao Yue, Xin Li, Chevaughn Smith, Xun Ai, Lixia Yue
Summary: TRPM4, a Ca2+-activated nonselective cation channel, plays a critical role in cardiac conduction and could be upregulated in heart failure patients, especially in cardiac fibroblasts. This upregulation may contribute to cardiac fibrogenesis under various pathological conditions.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Review
Biology
Ting Liu, Tao Li, Dandi Xu, Yan Wang, Yafei Zhou, Juyi Wan, Christopher L. -H. Huang, Xiaoqiu Tan
Summary: Ca2+-activated K+ channels play a critical role in cellular Ca2+ homeostasis and excitability by coupling intracellular Ca2+ and membrane voltage change. Among these channels, the SK channels, with small conductance and three subtypes, SK1/KCa2.1, SK2/KCa2.2, and SK3/KCa2.3, are expressed in various cardiomyocytes and show specific sensitivities to apamin. SK channels regulate action potential durations and effective refractory periods, potentially affecting arrhythmic tendency. Additionally, mitochondrial SK channels may mitigate mitochondrial Ca2+ overload and reactive oxygen species generation. SK channels exhibit low voltage but significant Ca2+ dependences, and their function relies on complex trafficking, expression processes, and associations with other ion channels or subunits from different SK subtypes. Clinical arrhythmogenesis in atrial and ventricular tissues can be influenced by altered SK expression, leading to changes in re-entrant rotors or triggered activity.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Anna Borgstrom, Christine Peinelt, Paulina Stoklosa
Summary: TRPM4, widely expressed in various organs, is associated with cardiovascular and immune diseases, and its role in cancer is gaining attention. Overexpression of TRPM4 has been observed in several types of cancer, indicating its potential as a prognostic marker and drug target. Further investigations are needed to understand the mechanisms by which TRPM4 contributes to cancer hallmark functions.
Article
Chemistry, Medicinal
Zsigmond Mate Kovacs, Csaba Dienes, Tamas Hezso, Janos Almassy, Janos Magyar, Tamas Banyasz, Peter P. Nanasi, Balazs Horvath, Norbert Szentandrassy
Summary: This review discusses the pharmacological modulation of TRPM4, as well as the methods and functions of studying TRPM4.
Article
Chemistry, Medicinal
Csaba Dienes, Zsigmond Mate Kovacs, Tamas Hezso, Janos Almassy, Janos Magyar, Tamas Banyasz, Peter P. Nanasi, Balazs Horvath, Norbert Szentandrassy
Summary: TRPM4 is a member of the TRPM protein family that regulates membrane potential and Ca2+ homeostasis. It is widely expressed in multiple organs and involved in various physiological functions, as well as contributing to pathological conditions.
