ArticleThe Journal of biological chemistry2010
Identification of a thiol/disulfide redox switch in the human BK channel that controls its affinity for heme and CO.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 81 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Article
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- Physiological oxygen levels reset KRedox biology · 2026Article
- Cytochrome C-like Domain Within the Human BK Channel.International journal of molecular sciences · 2025Article
- Article
- Redox Regulation of KAntioxidants & redox signaling · 2024Review
- Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024Review
- Article
- Redox-dependent CdBiophysical journal · 2024Article
- Redox Regulation of Mitochondrial Potassium Channels Activity.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- External Hemin as an Inhibitor of Mitochondrial Large-Conductance Calcium-Activated Potassium Channel Activity.International journal of molecular sciences · 2022Article
- Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response.Pharmacological reviews · 2022Review
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- Review
- Oxygen-dependent regulation of ion channels: acute responses, post-translational modification, and response to chronic hypoxia.Pflugers Archiv : European journal of physiology · 2021Review
- The role of brain gaseous neurotransmitters in anxiety.Pharmacological reports : PR · 2021Review
- ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels.Frontiers in pharmacology · 2021Article
- Discovery of a heme-binding domain in a neuronal voltage-gated potassium channel.The Journal of biological chemistry · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Heme is a required prosthetic group in many electron transfer proteins and redox enzymes. The human BK channel, which is a large-conductance Ca(2+) and voltage-activated K(+) channel, is involved in the hypoxic response in the carotid body. The BK channel has been shown to bind and undergo inhibition by heme and activation by CO. Furthermore, evidence suggests that human heme oxygenase-2 (HO2) acts as an oxygen sensor and CO donor that can form a protein complex with the BK channel. Here we describe a thiol/disulfide redox switch in the human BK channel and biochemical experiments of heme, CO, and HO2 binding to a 134-residue region within the cytoplasmic domain of the channel. This region, called the heme binding domain (HBD) forms a linker segment between two Ca(2+)-sensing domains (called RCK1 and RCK2) of the BK channel. The HBD includes a CXXCH motif in which histidine serves as the axial heme ligand and the two cysteine residues can form a reversible thiol/disulfide redox switch that regulates affinity of the HBD for heme. The reduced dithiol state binds heme (K(d) = 210 nm) 14-fold more tightly than the oxidized disulfide state. Furthermore, the HBD is shown to tightly bind CO (K(d) = 50 nm) with the Cys residues in the CXXCH motif regulating affinity of the HBD for CO. This HBD is also shown to interact with heme oxygenase-2. We propose that the thiol/disulfide switch in the HBD is a mechanism by which activity of the BK channel can respond quickly and reversibly to changes in the redox state of the cell, especially as it switches between hypoxic and normoxic conditions.
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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.