Trpm2, also known as transient receptor potential melastatin 2, is an oxidant-activated non-selective cation channel [2]. It functions as an endogenous redox sensor, mediating oxidative stress/ROS-induced Ca(2+) entry and subsequent Ca(2+)-dependent cellular reactions like endothelial hyperpermeability and apoptosis [2]. It is widely expressed in mammalian tissues, including the vascular endothelium [2]. Oxidative stress stimulates intracellular ADP-ribose formation which opens TRPM2 channels [2]. 2'-Deoxyadenosine 5'-diphosphoribose is an endogenous TRPM2 superagonist, which may act as a cell signaling molecule [3].

In the context of acute myocardial infarction (AMI), knockout of Trpm2 protected against myocardial injury and led to upregulation of clusterin (CLU) [1]. In H9C2 cells under hypoxic conditions, silencing of Trpm2 increased cell viability and decreased its own expression [1]. This indicates that Trpm2 may play a role in myocardial injury during AMI, and its knockout can have a protective effect [1].

In conclusion, Trpm2 is a crucial non-selective cation channel involved in redox-mediated Ca(2+) signaling. Its knockout in mouse models reveals its role in myocardial injury during AMI, suggesting that understanding Trpm2 function can potentially lead to new treatment strategies for AMI.

References:

1. Li, Dalei, Wang, Mengying, Fan, Rong, Gan, Hailin, Fan, Huaying. 2023. Clusterin regulates TRPM2 to protect against myocardial injury induced by acute myocardial infarction injury. In Tissue & cell, 82, 102038. doi:10.1016/j.tice.2023.102038. https://pubmed.ncbi.nlm.nih.gov/36870313/

2. Hecquet, Claudie M, Malik, Asrar B. . Role of H(2)O(2)-activated TRPM2 calcium channel in oxidant-induced endothelial injury. In Thrombosis and haemostasis, 101, 619-25. doi:. https://pubmed.ncbi.nlm.nih.gov/19350103/

3. Fliegert, Ralf, Bauche, Andreas, Wolf Pérez, Adriana-Michelle, Potter, Barry V L, Guse, Andreas H. 2017. 2'-Deoxyadenosine 5'-diphosphoribose is an endogenous TRPM2 superagonist. In Nature chemical biology, 13, 1036-1044. doi:10.1038/nchembio.2415. https://pubmed.ncbi.nlm.nih.gov/28671679/