ArticlePflugers Archiv : European journal of physiology2014
5,6-EET potently inhibits T-type calcium channels: implication in the regulation of the vascular tone.
Article in Pflugers Archiv : European journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension.Cardiovascular drugs and therapy · 2025Review
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- Review
- Endothelial deletion of the cytochrome P450 reductase leads to cardiac remodelling.Frontiers in physiology · 2022Article
- Epoxy Fatty Acids: From Salt Regulation to Kidney and Cardiovascular Therapeutics: 2019 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Neuronal Cav3 channelopathies: recent progress and perspectives.Pflugers Archiv : European journal of physiology · 2020Review
- TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway.Journal of molecular neuroscience : MN · 2019Article
- Oxidized Lipids in Persistent Pain States.Frontiers in pharmacology · 2019Review
- Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes.International journal of molecular sciences · 2018Review
- Deletion of T-type calcium channels CaPflugers Archiv : European journal of physiology · 2018Article
- Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.Frontiers in physiology · 2017Review
- Modulation of T-type calcium channels by bioactive lipids.Pflugers Archiv : European journal of physiology · 2014Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-type calcium channels (T-channels) are important actors in neuronal pacemaking, in heart rhythm, and in the control of the vascular tone. T-channels are regulated by several endogenous lipids including the primary eicosanoid arachidonic acid (AA), which display an important role in vasodilation via its metabolism leading to prostanoids, leukotrienes, and epoxyeicosatrienoic acids (EETs). However, the effects of these latter molecules on T-currents have not been investigated. Here, we describe the effects of the major cyclooxygenase, lipoxygenase, and cytochrome P450 epoxygenase products on the three human recombinant T-channels (Cav3.1, Cav3.2, and Cav3.3), as compared to those of AA. We identified the P450 epoxygenase product, 5,6-EET, as a potent physiological inhibitor of Cav3 currents. The effects of 5,6-EET were observed at sub-micromolar concentrations (IC50 = 0.54 μM), occurred in the minute range, and were reversible. The 5,6-EET inhibited the Cav3 currents at physiological resting membrane potentials mostly by inducing a large negative shift in their steady-state inactivation properties. Using knockout mice for Cav3.1 and Cav3.2, we demonstrated that the vasodilation of preconstricted mesenteric arteries induced by 5,6-EET was specifically impaired in Cav3.2 knockout mice. Overall, our results indicate that inhibition of Cav3 currents by 5,6-EET is an important mechanism controlling the vascular tone.
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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.