ArticleAmerican journal of physiology. Heart and circulatory physiology2015
Ca²⁺ entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Atrial TRPM2 Channel-Mediated CaCells · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Improving effect of physical exercise on heart failure: Reducing oxidative stress-induced inflammation by restoring CaMolecular and cellular biochemistry · 2025Review
- TRPM2 overactivation drives hyperlipidemia-induced dysfunction of myeloid cells and neurovascular units.Cell reports. Medicine · 2025Article
- TRPM2 knockdown attenuates myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice via regulating the MEK/ERK and mTORC1 signaling pathway.Molecular and cellular biochemistry · 2024Article
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- TRPM2 Mediates Hepatic Ischemia-Reperfusion Injury via CaResearch (Washington, D.C.) · 2023Article
- Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7.Frontiers in cell and developmental biology · 2023Review
- TRPM2: bridging calcium and ROS signaling pathways-implications for human diseases.Frontiers in physiology · 2023Review
- The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression.Scientific reports · 2022Article
- Amantadine Attenuated Hypoxia-Induced Mitochondrial Oxidative Neurotoxicity, Apoptosis, and Inflammation via the Inhibition of TRPM2 and TRPV4 Channels.Molecular neurobiology · 2022Article
- The human ion channel TRPM2 modulates cell survival in neuroblastoma through E2F1 and FOXM1.Scientific reports · 2022Article
- TRPM2 Non-Selective Cation Channels in Liver Injury Mediated by Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2021Review
- Calcium and Heart Failure: How Did We Get Here and Where Are We Going?International journal of molecular sciences · 2021Review
- Ethyl isopropyl amiloride decreases oxidative phosphorylation and increases mitochondrial fusion in clonal untransformed and cancer cells.American journal of physiology. Cell physiology · 2021Article
- Article
- Systematic Understanding of Pathophysiological Mechanisms of Oxidative Stress-Related Conditions-Diabetes Mellitus, Cardiovascular Diseases, and Ischemia-Reperfusion Injury.Frontiers in cardiovascular medicine · 2021Review
- Intracellular calcium leak in heart failure and atrial fibrillation: a unifying mechanism and therapeutic target.Nature reviews. Cardiology · 2020Review
- TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions.Redox biology · 2020Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Ubiquitously expressed Trpm2 channel limits oxidative stress and preserves mitochondrial function. We first demonstrated that intracellular Ca(2+) concentration increase after Trpm2 activation was due to direct Ca(2+) influx and not indirectly via reverse Na(+)/Ca(2+) exchange. To elucidate whether Ca(2+) entry via Trpm2 is required to maintain cellular bioenergetics, we injected adenovirus expressing green fluorescent protein (GFP), wild-type (WT) Trpm2, and loss-of-function (E960D) Trpm2 mutant into left ventricles of global Trpm2 knockout (gKO) or WT hearts. Five days post-injection, gKO-GFP heart slices had higher reactive oxygen species (ROS) levels but lower oxygen consumption rate (OCR) than WT-GFP heart slices. Trpm2 but not E960D decreased ROS and restored OCR in gKO hearts back to normal levels. In gKO myocytes expressing Trpm2 or its mutants, Trpm2 but not E960D reduced the elevated mitochondrial superoxide (O2(.-)) levels in gKO myocytes. After hypoxia-reoxygenation (H/R), Trpm2 but not E906D or P1018L (inactivates Trpm2 current) lowered O2(.-) levels in gKO myocytes and only in the presence of extracellular Ca(2+), indicating sustained Ca(2+) entry is necessary for Trpm2-mediated preservation of mitochondrial function. After ischemic-reperfusion (I/R), cardiac-specific Trpm2 KO hearts exhibited lower maximal first time derivative of LV pressure rise (+dP/dt) than WT hearts in vivo. After doxorubicin treatment, Trpm2 KO mice had worse survival and lower +dP/dt. We conclude 1) cardiac Trpm2-mediated Ca(2+) influx is necessary to maintain mitochondrial function and protect against H/R injury; 2) Ca(2+) influx via cardiac Trpm2 confers protection against H/R and I/R injury by reducing mitochondrial oxidants; and 3) Trpm2 confers protection in doxorubicin cardiomyopathy.
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