ArticleThe Journal of biological chemistry2014
Negatively charged amino acids near and in transient receptor potential (TRP) domain of TRPM4 channel are one determinant of its Ca2+ sensitivity.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 29 citations in OpenAlex.
- Structural landscape of activation, desensitization and inhibition in the human TRPM4 channel.Nature structural & molecular biology · 2026Article
- The TRP channels serving as chemical-to-electrical signal converter.Physiological reviews · 2025Review
- The role and mechanism of vascular wall cell ion channels in vascular fibrosis remodeling.Channels (Austin, Tex.) · 2024Review
- 2'-deoxy-ADPR activates human TRPM2 faster than ADPR and thereby induces higher currents at physiological CaFrontiers in immunology · 2024Article
- Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation.International journal of molecular sciences · 2023Review
- Biocompatibility of graphene oxide nanosheets functionalized with various amino acids towards mesenchymal stem cells.Heliyon · 2023Article
- A novel methylated cation channel TRPM4 inhibited colorectal cancer metastasis through CaInternational journal of biological sciences · 2022Article
- TRPM4 Conductances in Thalamic Reticular Nucleus Neurons Generate Persistent Firing during Slow Oscillations.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- TRPM4 and TRPM5 Channels Share Crucial Amino Acid Residues for CaInternational journal of molecular sciences · 2019Article
- Case Report: Investigation and molecular genetic diagnosis of familial hypomagnesaemia.F1000Research · 2019Article
- CaInternational journal of molecular sciences · 2018Review
- Structure of the human TRPM4 ion channel in a lipid nanodisc.Science (New York, N.Y.) · 2018Article
- Article
- Activation of Human Transient Receptor Potential Melastatin-8 (TRPM8) by Calcium-Rich Particulate Materials and Effects on Human Lung Cells.Molecular pharmacology · 2017Article
- Regulation of thermoTRPs by lipids.Temperature (Austin, Tex.) · 2017Review
- The unique electrical properties in an extracellular fluid of the mammalian cochlea; their functional roles, homeostatic processes, and pathological significance.Pflugers Archiv : European journal of physiology · 2016Review
- Novel Alleles of gon-2, a C. elegans Ortholog of Mammalian TRPM6 and TRPM7, Obtained by Genetic Reversion Screens.PloS one · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient receptor potential (TRP) channel melastatin subfamily member 4 (TRPM4) is a broadly expressed nonselective monovalent cation channel. TRPM4 is activated by membrane depolarization and intracellular Ca(2+), which is essential for the activation. The Ca(2+) sensitivity is known to be regulated by calmodulin and membrane phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Although these regulators must play important roles in controlling TRPM4 activity, mutation analyses of the calmodulin-binding sites have suggested that Ca(2+) binds to TRPM4 directly. However, the intrinsic binding sites in TRPM4 remain to be elucidated. Here, by using patch clamp and molecular biological techniques, we show that there are at least two functionally different divalent cation-binding sites, and the negatively charged amino acids near and in the TRP domain in the C-terminal tail of TRPM4 (Asp-1049 and Glu-1062 of rat TRPM4) are required for maintaining the normal Ca(2+) sensitivity of one of the binding sites. Applications of Co(2+), Mn(2+), or Ni(2+) to the cytosolic side potentiated TRPM4 currents, increased the Ca(2+) sensitivity, but were unable to evoke TRPM4 currents without Ca(2+). Mutations of the acidic amino acids near and in the TRP domain, which are conserved in TRPM2, TRPM5, and TRPM8, deteriorated the Ca(2+) sensitivity in the presence of Co(2+) or PI(4,5)P2 but hardly affected the sensitivity to Co(2+) and PI(4,5)P2. These results suggest a novel role of the TRP domain in TRPM4 as a site responsible for maintaining the normal Ca(2+) sensitivity. These findings provide more insights into the molecular mechanisms of the regulation of TRPM4 by Ca(2+).
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