ArticleThe Journal of physiology2004
Decavanadate modulates gating of TRPM4 cation channels.
Article in The Journal of physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 124 citations in OpenAlex.
- Role of TRPM4 ion channel in pediatric arrhythmic syndromes.World journal of clinical pediatrics · 2026Review
- Temperature and intrinsic CaNature structural & molecular biology · 2026Article
- Heat- and PIP2-dependent TRPM4 activity underlies mutually exclusive human diseases.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Noncanonical calcium-independent TRPM4 activation governs intestinal fluid homeostasis.Nature communications · 2026Article
- Structural biology of the TRPM4 channel: architecture, modulation, and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Review
- The TRP channels serving as chemical-to-electrical signal converter.Physiological reviews · 2025Review
- TRPM3, TRPM4, and TRPM5 as thermo-sensitive channels.The journal of physiological sciences : JPS · 2024Review
- Article
- Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation.International journal of molecular sciences · 2023Review
- Article
- Article
- Polyoxovanadates as new P-glycoprotein inhibitors: insights into the mechanism of inhibition.FEBS letters · 2022Article
- Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel-Part 1: Modulation of TRPM4.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition.Nature structural & molecular biology · 2021Article
- IInternational journal of molecular sciences · 2021Article
- Upregulation of transient receptor potential melastatin 4 (TRPM4) in ventricular fibroblasts from heart failure patients.Pflugers Archiv : European journal of physiology · 2021Article
- Species-Specific Effects of Cation Channel TRPM4 Small-Molecule Inhibitors.Frontiers in pharmacology · 2021Article
- Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling.Comprehensive Physiology · 2019Review
- Trpm4 ion channels in pre-Bötzinger complex interneurons are essential for breathing motor pattern but not rhythm.PLoS biology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have tested the effects of decavanadate (DV), a compound known to interfere with ATP binding in ATP-dependent transport proteins, on TRPM4, a Ca(2+)-activated, voltage-dependent monovalent cation channel, whose activity is potently blocked by intracellular ATP(4-). Application of micromolar Ca(2+) concentrations to the cytoplasmic side of inside-out patches led to immediate current activation followed by rapid current decay, which can be explained by an at least 30-fold decreased apparent affinity for Ca(2+). Subsequent application of DV (10 microm) strongly affected the voltage-dependent gating of the channel, resulting in large sustained currents over the voltage range between -180 and +140 mV. The effect of DV was half-maximal at a concentration of 1.9 microm. The Ca(2+)- and voltage-dependent gating of the channel was well described by a sequential kinetic scheme in which Ca(2+) binding precedes voltage-dependent gating. The effects of DV could be explained by an action on the voltage-dependent closing step. Surprisingly, DV did not antagonize the effect of ATP(4-) on TRPM4, but caused a nearly 10-fold increase in the sensitivity of the ATP(4-) block. TRPM5, which is the most homologous channel to TRPM4, was not modulated by DV. The effect of DV was lost in a TRPM4 chimera in which the C-terminus was substituted with that of TRPM5. Deletion of a cluster in the C-terminus of TRPM4 containing positively charged amino acid residues with a high homology to part of the decavanadate binding site in SERCA pumps, completely abolished the DV effect but also accelerated desensitization. Deletion of a similar site in the N-terminus had no effects on DV responses. These results indicate that the C-terminus of TRPM4 is critically involved in mediating the DV effects. In conclusion, decavanadate modulates TRPM4, but not TRPM5, by inhibiting voltage-dependent closure of the channel.
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