ArticleThe Journal of biological chemistry2011
Molecular basis and structural insight of vascular K(ATP) channel gating by S-glutathionylation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- [Exogenous nitric oxide suppresses KSheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2026Article
- Redox Regulation of KAntioxidants & redox signaling · 2024Review
- Modulatory Impact of Oxidative Stress on Action Potentials in Pathophysiological States: A Comprehensive Review.Antioxidants (Basel, Switzerland) · 2024Review
- Redox Regulation of Mitochondrial Potassium Channels Activity.Antioxidants (Basel, Switzerland) · 2024Review
- Oxidative stress and ion channels in neurodegenerative diseases.Frontiers in physiology · 2024Review
- The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients.Frontiers in neuroscience · 2024Review
- Oxidation Driven Reversal of PIPFunction (Oxford, England) · 2023Article
- Kir6.1 and SUR2B in Cantú syndrome.American journal of physiology. Cell physiology · 2022Review
- Metabolic Shades of S-D-Lactoylglutathione.Antioxidants (Basel, Switzerland) · 2022Review
- Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders.European psychiatry : the journal of the Association of European Psychiatrists · 2020Review
- Redox Regulation of Ion Channels and Receptors in Pulmonary Hypertension.Antioxidants & redox signaling · 2019Review
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- Contribution of KCirculation research · 2017Article
- Biological chemistry and functionality of protein sulfenic acids and related thiol modifications.Free radical research · 2016Review
- Redox regulation of ion channels in the pulmonary circulation.Antioxidants & redox signaling · 2015Review
- Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation.Pflugers Archiv : European journal of physiology · 2015Article
- Postranslational Modification of Ion Channels in Colonic Inflammation.Current neuropharmacology · 2015Review
- Glutathionylation of the L-type Ca2+ channel in oxidative stress-induced pathology of the heart.International journal of molecular sciences · 2014Review
- Depolarized inactivation overcomes impaired activation to produce DRG neuron hyperexcitability in a Nav1.7 mutation in a patient with distal limb pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The vascular ATP-sensitive K(+) (K(ATP)) channel is targeted by a variety of vasoactive substances, playing an important role in vascular tone regulation. Our recent studies indicate that the vascular K(ATP) channel is inhibited in oxidative stress via S-glutathionylation. Here we show evidence for the molecular basis of the S-glutathionylation and its structural impact on channel gating. By comparing the oxidant responses of the Kir6.1/SUR2B channel with the Kir6.2/SUR2B channel, we found that the Kir6.1 subunit was responsible for oxidant sensitivity. Oxidant screening of Kir6.1-Kir6.2 chimeras demonstrated that the N terminus and transmembrane domains of Kir6.1 were crucial. Systematic mutational analysis revealed three cysteine residues in these domains: Cys(43), Cys(120), and Cys(176). Among them, Cys(176) was prominent, contributing to >80% of the oxidant sensitivity. The Kir6.1-C176A/SUR2B mutant channel, however, remained sensitive to both channel opener and inhibitor, which indicated that Cys(176) is not a general gating site in Kir6.1, in contrast to its counterpart (Cys(166)) in Kir6.2. A protein pull-down assay with biotinylated glutathione ethyl ester showed that mutation of Cys(176) impaired oxidant-induced incorporation of glutathione (GSH) into the Kir6.1 subunit. In contrast to Cys(176), Cys(43) had only a modest contribution to S-glutathionylation, and Cys(120) was modulated by extracellular oxidants but not intracellular GSSG. Simulation modeling of Kir6.1 S-glutathionylation suggested that after incorporation to residue 176, the GSH moiety occupied a space between the slide helix and two transmembrane helices. This prevented the inner transmembrane helix from undergoing conformational changes necessary for channel gating, retaining the channel in its closed state.
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