ArticleThe Journal of biological chemistry2010
State-dependent inhibition of TRPM2 channel by acidic pH.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- 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
- Silencing TRPM2 enhanced erastin- and RSL3-induced ferroptosis in gastric cancer cells through destabilizing HIF-1α and Nrf2 proteins.Cytotechnology · 2022Article
- CaInternational journal of molecular sciences · 2022Review
- Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury.Neuron · 2022Article
- On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications.Frontiers in oncology · 2022Review
- The decrease in hippocampal transient receptor potential M2 (TRPM2) channel and muscarinic acetylcholine receptor 1 (CHRM1) is associated with memory loss in a surgical menopause rat model.Archives of medical science : AMS · 2021Article
- The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons.Frontiers in pharmacology · 2021Article
- Roles of NADMolecules (Basel, Switzerland) · 2020Review
- pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.Cancers · 2020Review
- TRPM2: a candidate therapeutic target for treating neurological diseases.Acta pharmacologica Sinica · 2018Review
- The role of TRPM2 channels in neurons, glial cells and the blood-brain barrier in cerebral ischemia and hypoxia.Acta pharmacologica Sinica · 2018Review
- TRPM2 channel-mediated regulation of autophagy maintains mitochondrial function and promotes gastric cancer cell survival via the JNK-signaling pathway.The Journal of biological chemistry · 2018Article
- Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues.Chemical biology & drug design · 2018Article
- Identification of a Novel EF-Loop in the N-terminus of TRPM2 Channel Involved in Calcium Sensitivity.Frontiers in pharmacology · 2018Article
- Ligand-induced activation of human TRPM2 requires the terminal ribose of ADPR and involves Arg1433 and Tyr1349.The Biochemical journal · 2017Article
- Extracellular protons enable activation of the calcium-dependent chloride channel TMEM16A.The Journal of physiology · 2017Article
- Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2.The Journal of general physiology · 2017Article
- The overexpressed functional transient receptor potential channel TRPM2 in oral squamous cell carcinoma.Scientific reports · 2016Article
- Detrimental or beneficial: the role of TRPM2 in ischemia/reperfusion injury.Acta pharmacologica Sinica · 2016Review
- Identification of key amino acid residues responsible for internal and external pH sensitivity of Orai1/STIM1 channels.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Transient receptor potential melastatin 2 (TRPM2) channel fulfills an important role in oxidative stress signaling in immune and other cells, to which local extracellular acidosis is known to occur under physiological or pathological conditions and impose significant effects on their functions. Here, we investigated whether the ADP-ribose-activated TRPM2 channel is a target for modulation by extracellular acidic pH by patch clamp recording of HEK293 cells expressing hTRPM2 channel. Induced whole cell or single channel currents were rapidly inhibited upon subsequent exposure to acidic pH. The inhibition in the steady state was complete, voltage-independent, and pH-independent in the range of pH 4.0-6.0. The inhibition was irreversible upon returning to pH 7.3, suggesting channel inactivation. In contrast, exposure of closed channels to acidic pH reduced the subsequent channel activation in a pH-dependent manner with an IC(50) for H(+) of 20 μm (pH 4.7) and rendered subsequent current inhibition largely reversible, indicating differential or state-dependent inhibition and inactivation. Alanine substitution of residues in the outer vestibule of the pore including Lys(952) and Asp(1002) significantly slowed down or reduced acidic pH-induced inhibition and prevented inactivation. The results suggest that acidic pH acts as a negative feedback mechanism where protons bind to the outer vestibule of the TRPM2 channel pore and inhibit the TRPM2 channels in a state-dependent manner.
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