ArticleThe Journal of general physiology2003
TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions.
Article in The Journal of general physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 264 papers, 1 of them a synthesis that pooled it.
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Who cites it
264 citing papers in PubMed, 1 synthesis or guideline pooled it, 514 citations in OpenAlex.
- Neuroprotective role of carvacrol in ischemic brain injury: a systematic review of preclinical evidence and proposed TRPM7 involvement.Frontiers in pharmacology · 2025Pooled it
- An update on regulation of the polymodal TRPV4 channel by protein phosphorylation.Channels (Austin, Tex.) · 2026Review
- TRPM7 kinase: a target for multimodal drug development in neurological disorders.Acta pharmacologica Sinica · 2026Review
- TRPM7 kinase inhibitor TG100-115 provides neuroprotection against neonatal hypoxic-ischemic brain injury.Acta pharmacologica Sinica · 2026Article
- TRPM7 Deficiency Protects Against Myocardial Ischemia-Reperfusion Injury by Regulating Intracellular ZnCirculation · 2026Article
- Chronic cadmium exposure promotes TRPM7-dependent acquisition of a myofibroblast-like phenotype in pancreatic stellate cells.Cell biology and toxicology · 2026Article
- Integrative phosphoproteomic analysis identifies functional roles of TRPM7 phosphosites in oncogenesis.Frontiers in bioinformatics · 2026Article
- Carvacrol improves neurological function by inhibiting TRPM7-mediated BBB disruption and hemorrhage after TBI.Acta neuropathologica communications · 2025Article
- Transient receptor melastatin channel in colorectal cancer: pathophysiological mechanisms and a promising drug target.Cancer chemotherapy and pharmacology · 2025Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRP Channels in Skin Cancer: Focus on Malignant Melanoma.International journal of molecular sciences · 2025Review
- TRPM7 underlies cadmium cytotoxicity in pulmonary cells.Archives of toxicology · 2025Article
- Simulated Microgravity Attenuates Stretch Sensitivity of Mechanically Gated Channels in Rat Ventricular Myocytes.International journal of molecular sciences · 2025Article
- Transient Receptor Potential Channels in Physiology and Pathophysiology: Special Issue.International journal of molecular sciences · 2025Article
- The TRPV3 channel is a mediator of zinc influx and homeostasis in murine oocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- MgScience advances · 2025Article
- The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease.International journal of molecular sciences · 2025Review
- Intracellular cAMP signaling-induced CaPflugers Archiv : European journal of physiology · 2025Article
- The TRPM7 chanzyme in smooth muscle cells drives abdominal aortic aneurysm in mice.Nature cardiovascular research · 2025Article
- Prebiotics as modulators of colonic calcium and magnesium uptake.Acta physiologica (Oxford, England) · 2025Review
204 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Trace metal ions such as Zn(2+), Fe(2+), Cu(2+), Mn(2+), and Co(2+) are required cofactors for many essential cellular enzymes, yet little is known about the mechanisms through which they enter into cells. We have shown previously that the widely expressed ion channel TRPM7 (LTRPC7, ChaK1, TRP-PLIK) functions as a Ca(2+)- and Mg(2+)-permeable cation channel, whose activity is regulated by intracellular Mg(2+) and Mg(2+).ATP and have designated native TRPM7-mediated currents as magnesium-nucleotide-regulated metal ion currents (MagNuM). Here we report that heterologously overexpressed TRPM7 in HEK-293 cells conducts a range of essential and toxic divalent metal ions with strong preference for Zn(2+) and Ni(2+), which both permeate TRPM7 up to four times better than Ca(2+). Similarly, native MagNuM currents are also able to support Zn(2+) entry. Furthermore, TRPM7 allows other essential metals such as Mn(2+) and Co(2+) to permeate, and permits significant entry of nonphysiologic or toxic metals such as Cd(2+), Ba(2+), and Sr(2+). Equimolar replacement studies substituting 10 mM Ca(2+) with the respective divalent ions reveal a unique permeation profile for TRPM7 with a permeability sequence of Zn(2+) approximately Ni(2+) >> Ba(2+) > Co(2+) > Mg(2+) >/= Mn(2+) >/= Sr(2+) >/= Cd(2+) >/= Ca(2+), while trivalent ions such as La(3+) and Gd(3+) are not measurably permeable. With the exception of Mg(2+), which exerts strong negative feedback from the intracellular side of the pore, this sequence is faithfully maintained when isotonic solutions of these divalent cations are used. Fura-2 quenching experiments with Mn(2+), Co(2+), or Ni(2+) suggest that these can be transported by TRPM7 in the presence of physiological levels of Ca(2+) and Mg(2+), suggesting that TRPM7 represents a novel ion-channel mechanism for cellular metal ion entry into vertebrate cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.