ArticlePflugers Archiv : European journal of physiology2016
Mibefradil represents a new class of benzimidazole TRPM7 channel agonists.
Article in Pflugers Archiv : European journal of physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Functional model for amelogenesis: polarization and pH sensitivity of calcium uptake in ameloblast-derived HAT-7 cells.Calcified tissue international · 2026Article
- TRPM7 in Peripheral and Central Immune Cells: Emerging Roles in Neuroinflammation and Neurological Disease.International journal of molecular sciences · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRPM7 underlies cadmium cytotoxicity in pulmonary cells.Archives of toxicology · 2025Article
- Molecular Mechanism of Oil-Infused Silicone Preventing Mussel Biofouling.Research (Washington, D.C.) · 2025Article
- Altered TRPM7-Dependent Calcium Influx in Natural Killer Cells of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.Biomolecules · 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
- Article
- Expression ofFrontiers in pediatrics · 2022Article
- Mibefradil alters intracellular calcium concentration by activation of phospholipase C and IPMolecular biomedicine · 2021Article
- TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts.International journal of molecular sciences · 2021Article
- Role of TRPM7 in cardiac fibrosis: A potential therapeutic target (Review).Experimental and therapeutic medicine · 2021Review
- Mapping TRPM7 Function by NS8593.International journal of molecular sciences · 2020Review
- Regulation of [CaReproductive biology and endocrinology : RB&E · 2020Article
- TRPM7 activation potentiates SOCE in enamel cells but requires ORAI.Cell calcium · 2020Article
- Mibefradil, a T-type CaBritish journal of pharmacology · 2019Article
- Functional expression of the mechanosensitive PIEZO1 channel in primary endometrial epithelial cells and endometrial organoids.Scientific reports · 2019Article
- TRPM7 and CaProceedings of the National Academy of Sciences of the United States of America · 2018Article
- TRPM6 and TRPM7 differentially contribute to the relief of heteromeric TRPM6/7 channels from inhibition by cytosolic MgScientific reports · 2017Article
- The calcium-cancer signalling nexus.Nature reviews. Cancer · 2017Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a bi-functional protein comprising an ion channel moiety covalently linked to a protein kinase domain. Currently, the prevailing view is that a decrease in the cytosolic Mg(2+) concentration leads to activation of divalent cation-selective TRPM7 currents. TRPM7 plays a role in immune responses, hypotension, tissue fibrosis, and tumor progression and, therefore, represents a new promising therapeutic target. Because of the dearth of pharmacological tools, our mechanistic understanding of the role of TRPM7 in physiology and pathophysiology still lags behind. Therefore, we have recently carried out a high throughput screen for small-molecule activators of TRPM7. We have characterized the phenanthrene naltriben as a first stimulatory agonist of the TRPM7 channel. Surprisingly, the effect of naltriben on TRPM7 was found to be unaffected by the physiological levels of cytosolic Mg(2+). Here, we demonstrate that mibefradil and NNC 50-0396, two benzimidazole relatives of the TRPM7 inhibitor NS8593, are positive modulators of TRPM7. Using Ca(2+) imaging and the patch-clamp technique, we show that mibefradil activates TRPM7-mediated Ca(2+) entry and whole-cell currents. The response to mibefradil was fast, reversible, and reproducible. In contrast to naltriben, mibefradil efficiently activates TRPM7 currents only at physiological intracellular Mg(2+) concentrations, and its stimulatory effect was fully abrogated by high internal Mg(2+) levels. Consequently, a TRPM7 variant harboring a gain-of-function mutation was insensitive to further mibefradil activation. Finally, we observed that the effect of mibefradil was selective for TRPM7 when various TRP channels were tested. Taken together, mibefradil acts as a Mg(2+)-regulated agonist of the TRPM7 channel and, hence, uncovers a new class of TRPM7 agonists.
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