ArticleThe Journal of biological chemistry2011
Zinc inactivates melastatin transient receptor potential 2 channels via the outer pore.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.BMC cancer · 2025Article
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- TRPM2 Channel Inhibition Attenuates Amyloid β42-Induced Apoptosis and Oxidative Stress in the Hippocampus of Mice.Cellular and molecular neurobiology · 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
- The crystal structure of TRPM2 MHR1/2 domain reveals a conserved ZnProtein science : a publication of the Protein Society · 2022Article
- On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications.Frontiers in oncology · 2022Review
- The identification of the key residues E829 and R845 involved in transient receptor potential melastatin 2 channel gating.Frontiers in aging neuroscience · 2022Article
- TRPM2 Non-Selective Cation Channels in Liver Injury Mediated by Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2021Review
- Roles of NADMolecules (Basel, Switzerland) · 2020Review
- TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions.Redox biology · 2020Review
- The role of TRPM2 channels in neurons, glial cells and the blood-brain barrier in cerebral ischemia and hypoxia.Acta pharmacologica Sinica · 2018Review
- Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons.Cell death & disease · 2018Article
- Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues.Chemical biology & drug design · 2018Article
- Signalling mechanisms mediating ZnScientific reports · 2017Article
- Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2.The Journal of general physiology · 2017Article
- Alteration in Intracellular ZnFrontiers in molecular neuroscience · 2017Article
- The overexpressed functional transient receptor potential channel TRPM2 in oral squamous cell carcinoma.Scientific reports · 2016Article
- Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins.International journal of molecular sciences · 2016Review
- Detrimental or beneficial: the role of TRPM2 in ischemia/reperfusion injury.Acta pharmacologica Sinica · 2016Review
- Copper-Induced Membrane Depolarizations Involve the Induction of Mosaic TRP Channels, Which Activate VDCC Leading to Calcium Increases in Ulva compressa.Frontiers in plant science · 2016Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zinc ion (Zn(2+)) is an endogenous allosteric modulator that regulates the activity of a wide variety of ion channels in a reversible and concentration-dependent fashion. Here we used patch clamp recording to study the effects of Zn(2+) on the melastatin transient receptor potential 2 (TRPM2) channel. Zn(2+) inhibited the human (h) TRPM2 channel currents, and the steady-state inhibition was largely not reversed upon washout and concentration-independent in the range of 30-1000 μM, suggesting that Zn(2+) induces channel inactivation. Zn(2+) inactivated the channels fully when they conducted inward currents, but only by half when they passed outward currents, indicating profound influence of the permeant ion on Zn(2+) inactivation. Alanine substitution scanning mutagenesis of 20 Zn(2+)-interacting candidate residues in the outer pore region of the hTRPM2 channel showed that mutation of Lys(952) in the extracellular end of the fifth transmembrane segment and Asp(1002) in the large turret strongly attenuated or abolished Zn(2+) inactivation, and mutation of several other residues dramatically changed the inactivation kinetics. The mouse (m) TRPM2 channels were also inactivated by Zn(2+), but the kinetics were remarkably slower. Reciprocal mutation of His(995) in the hTRPM2 channel and the equivalent Gln(992) in the mTRPM2 channel completely swapped the kinetics, but no such opposing effects resulted from exchanging another pair of species-specific residues, Arg(961)/Ser(958). We conclude from these results that Zn(2+) inactivates the TRPM2 channels and that residues in the outer pore are critical determinants of the inactivation.
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