ArticleScience signaling2015
Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 164 citations in OpenAlex.
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026Review
- TMEM16A channel signalling microdomains in the regulation of vascular function.The Journal of physiology · 2026Review
- Brain Capillary Ion Channels: Physiology and Channelopathies.Physiology (Bethesda, Md.) · 2026Review
- Role of TRP channels in lymphatic function.Frontiers in physiology · 2026Review
- Microtubule-Dependent CaJournal of the American Heart Association · 2025Article
- TRP channels and cancer modulation: a voyage beyond metabolic reprogramming, oxidative stress and the advent of nanotechnologies in targeted therapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Effects of SGLT2 inhibitors on ion channels in heart failure: focus on the endothelium.Basic research in cardiology · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Molecular Principles of Proton-Coupled Quinone Reduction in the Membrane-Bound Superoxide Oxidase.Journal of the American Chemical Society · 2025Article
- Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Hydrogen Sulfide-induced CaCurrent neuropharmacology · 2025Article
- The ion transport, GPCR, and RTK toolkit expression in the human cerebrovascular endothelial cell line, hCMEC/D3: an Omics perspective.Frontiers in physiology · 2025Article
- Effects of Hydrogen Sulfide at Normal Body Temperature and in the Cold on Isolated Tail and Carotid Arteries from Rats and TRPA1 Knockout and Wild-Type Mice.Biomedicines · 2024Article
- The TRPA1 Ion Channel Mediates Oxidative Stress-Related Migraine Pathogenesis.Molecules (Basel, Switzerland) · 2024Review
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- Ion Channel Dysregulation Following Intracerebral Hemorrhage.Neuroscience bulletin · 2024Review
- Mechanosensing by Vascular Endothelium.Annual review of physiology · 2024Review
- Electro-metabolic signaling.The Journal of general physiology · 2024Article
- The conducted vasomotor response and the principles of electrical communication in resistance arteries.Physiological reviews · 2024Review
- Mechanosensory entities and functionality of endothelial cells.Frontiers in cell and developmental biology · 2024Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca(2+)-permeable transient receptor potential ankyrin 1 (TRPA1) channels were present and colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source of ROS, in the endothelium of cerebral arteries but not in other vascular beds. We recorded and characterized ROS-triggered Ca(2+) signals representing Ca(2+) influx through single TRPA1 channels, which we called "TRPA1 sparklets." TRPA1 sparklet activity was low under basal conditions but was stimulated by NOX-generated ROS. Ca(2+) entry during a single TRPA1 sparklet was twice that of a TRPV4 sparklet and ~200 times that of an L-type Ca(2+) channel sparklet. TRPA1 sparklets representing the simultaneous opening of two TRPA1 channels were more common in endothelial cells than in human embryonic kidney (HEK) 293 cells expressing TRPA1. The NOX-induced TRPA1 sparklets activated intermediate-conductance, Ca(2+)-sensitive K(+) channels, resulting in smooth muscle hyperpolarization and vasodilation. NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries. These data suggest that in the cerebral circulation, lipid peroxidation metabolites generated by ROS activate Ca(2+) influx through TRPA1 channels in the endothelium of cerebral arteries to cause dilation.
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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.