ArticleThe Journal of biological chemistry2008
Carbon monoxide inhibits L-type Ca2+ channels via redox modulation of key cysteine residues by mitochondrial reactive oxygen species.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Pooled it
- CO-mediated restoration of mitochondrial redox homeostasis contributes to alleviating multiple programmed cell deaths in hepatic I/R injury.Redox biology · 2026Article
- Antinociceptive Effects of Exogenous and Endogenous Carbon Monoxide in the Nitroglycerin-Induced Migraine Model in Rats.International journal of molecular sciences · 2026Article
- Recent advances in the role of gasotransmitters in necroptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- Structure-Photoreactivity Relationship Study of Substituted 3-Hydroxyflavones and 3-Hydroxyflavothiones for Improving Carbon Monoxide Photorelease.The Journal of organic chemistry · 2024Article
- Recent progress on anti-nociceptive effects of carbon monoxide releasing molecule-2 (CORM-2).Molecular and cellular biochemistry · 2024Review
- Acute oxygen sensing by vascular smooth muscle cells.Frontiers in physiology · 2023Review
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response.Pharmacological reviews · 2022Review
- A TCF-Based Carbon Monoxide NIR-Probe without the Interference of BSA and Its Application in Living Cells.Molecules (Basel, Switzerland) · 2022Article
- Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System.International journal of molecular sciences · 2022Review
- Signaling pathways and targeted therapy for myocardial infarction.Signal transduction and targeted therapy · 2022Review
- Carbon monoxide activation of delayed rectifier potassium currents of human cardiac fibroblasts through diverse pathways.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Article
- Downregulation of Vascular Hemeoxygenase-1 Leads to Vasculopathy in Systemic Sclerosis.Frontiers in physiology · 2022Article
- Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite.Inorganic chemistry · 2021Review
- Air Pollution and Cardiac Arrhythmias: From Epidemiological and Clinical Evidences to Cellular Electrophysiological Mechanisms.Frontiers in cardiovascular medicine · 2021Review
- Carbon Monoxide (CO), Nitric Oxide, and Hydrogen Sulfide Signaling During Acute CO Poisoning.Frontiers in pharmacology · 2021Review
- Deterministic and Stochastic Cellular Mechanisms Contributing to Carbon Monoxide Induced Ventricular Arrhythmias.Frontiers in pharmacology · 2021Article
- Reactive Oxygen Species Modulate Activity-Dependent AMPA Receptor Transport inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Conditions of stress, such as myocardial infarction, stimulate up-regulation of heme oxygenase (HO-1) to provide cardioprotection. Here, we show that CO, a product of heme catabolism by HO-1, directly inhibits native rat cardiomyocyte L-type Ca2+ currents and the recombinant alpha1C subunit of the human cardiac L-type Ca2+ channel. CO (applied via a recognized CO donor molecule or as the dissolved gas) caused reversible, voltage-independent channel inhibition, which was dependent on the presence of a spliced insert in the cytoplasmic C-terminal region of the channel. Sequential molecular dissection and point mutagenesis identified three key cysteine residues within the proximal 31 amino acids of the splice insert required for CO sensitivity. CO-mediated inhibition was independent of nitric oxide and protein kinase G but was prevented by antioxidants and the reducing agent, dithiothreitol. Inhibition of NADPH oxidase and xanthine oxidase did not affect the inhibitory actions of CO. Instead, inhibitors of complex III (but not complex I) of the mitochondrial electron transport chain and a mitochondrially targeted antioxidant (Mito Q) fully prevented the effects of CO. Our data indicate that the cardioprotective effects of HO-1 activity may be attributable to an inhibitory action of CO on cardiac L-type Ca2+ channels. Inhibition arises from the ability of CO to promote generation of reactive oxygen species from complex III of mitochondria. This in turn leads to redox modulation of any or all of three critical cysteine residues in the channel's cytoplasmic C-terminal tail, resulting in channel inhibition.
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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.