ArticleBritish journal of pharmacology2007
The plasma membrane Na+/Ca2+ exchange inhibitor KB-R7943 is also a potent inhibitor of the mitochondrial Ca2+ uniporter.
Article in British journal of pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 92 citations in OpenAlex.
- ATL2 Recruits TRAK1 to Promote Mitochondrial Transport at ER-Mitochondria Contact Sites.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pacemaking in the lymphatic system.The Journal of physiology · 2026Review
- PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations.Circulation · 2025Article
- Supramolecular delivery of dinuclear ruthenium and osmium MCU inhibitors.Inorganic chemistry frontiers · 2024Article
- Calcium signaling from sarcoplasmic reticulum and mitochondria contact sites in acute myocardial infarction.Journal of translational medicine · 2024Review
- Investigation of Cobalt(III) Cage Complexes as Inhibitors of the Mitochondrial Calcium Uniporter.European journal of inorganic chemistry · 2023Article
- Dinuclear nitrido-bridged osmium complexes inhibit the mitochondrial calcium uniporter and protect cortical neurons against lethal oxygen-glucose deprivation.RSC chemical biology · 2023Article
- Carboxylate-Capped Analogues of Ru265 Are MCU Inhibitor Prodrugs.Inorganic chemistry · 2022Article
- A mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells.The Journal of cell biology · 2022Article
- Excitation-contraction coupling in mammalian skeletal muscle: Blending old and last-decade research.Frontiers in physiology · 2022Review
- Identification and functional validation of FDA-approved positive and negative modulators of the mitochondrial calcium uniporter.Cell reports · 2021Article
- Cobalt amine complexes and Ru265 interact with the DIME region of the mitochondrial calcium uniporter.Chemical communications (Cambridge, England) · 2021Article
- Targeting mitochondrial ion channels for cancer therapy.Redox biology · 2021Review
- Mitochondrial CaCells · 2021Review
- Update on Calcium Signaling in Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2021Review
- Thioridazine requires calcium influx to induce MLL-AF6-rearranged AML cell death.Blood advances · 2020Article
- Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts.Cell death & disease · 2020Article
- Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis.Science advances · 2020Article
- Mortalin/HSPA9 targeting selectively induces KRAS tumor cell death by perturbing mitochondrial membrane permeability.Oncogene · 2020Article
- Mortalin (HSPA9) facilitatesScience signaling · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe thiourea derivative KB-R7943, originally developed as inhibitor of the plasma membrane Na(+)/Ca(2+) exchanger, has been shown to protect against myocardial ischemia-reperfusion injury. We have studied here its effects on mitochondrial Ca(2+) fluxes. EXPERIMENTAL APPROACH: [Ca(2+)] in cytosol, mitochondria and endoplasmic reticulum (ER), and mitochondrial membrane potential were monitored using both luminescent (targeted aequorins) and fluorescent (fura-2, tetramethylrhodamine ethyl ester) probes in HeLa cells. KEY
resultsKB-R7943 was also a potent inhibitor of the mitochondrial Ca(2+) uniporter (MCU). In permeabilized HeLa cells, KB-R7943 inhibited mitochondrial Ca(2+) uptake with a Ki of 5.5+/-1.3 microM (mean+/-S.D.). In intact cells, 10 microM KB-R7943 reduced by 80% the mitochondrial [Ca(2+)] peak induced by histamine. KB-R7943 did not modify the mitochondrial membrane potential and had no effect on the mitochondrial Na(+)/Ca(2+) exchanger. KB-R7943 inhibited histamine-induced ER-Ca(2+) release in intact cells, but not in cells loaded with a Ca(2+)-chelator to damp cytosolic [Ca(2+)] changes. Therefore, inhibition of ER-Ca(2+)-release by KB-R7943 was probably due to the increased feedback Ca(2+)-inhibition of inositol 1,4,5-trisphosphate receptors after MCU block. This mechanism also explains why KB-R7943 reversibly blocked histamine-induced cytosolic [Ca(2+)] oscillations in the same range of concentrations required to inhibit MCU. CONCLUSIONS AND IMPLICATIONS: Inhibition of MCU by KB-R7943 may contribute to its cardioprotective activity by preventing mitochondrial Ca(2+)-overload during ischemia-reperfusion. In addition, the effects of KB-R7943 on Ca(2+) homeostasis provide new evidence for the role of mitochondria modulating Ca(2+)-release and regenerative Ca(2+)-oscillations. Search for permeable and selective MCU inhibitors may yield useful pharmacological tools in the future.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.