ArticleProceedings of the National Academy of Sciences of the United States of America2013
Convergent Ca2+ and Zn2+ signaling regulates apoptotic Kv2.1 K+ currents.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
- Abnormal cytoskeletal remodeling but normal neuronal excitability in a mouse model of the recurrent developmental and epileptic encephalopathy-susceptibility KCNB1-p.R312H variant.Communications biology · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Non-conducting functions of potassium channels in cancer and neurological disease.Current topics in membranes · 2023Review
- Non-conducting functions of ion channels: The case of integrin-ion channel complexes.Channels (Austin, Tex.) · 2022Review
- Mechanism of use-dependent Kv2 channel inhibition by RY785.The Journal of general physiology · 2022Article
- Altered neural cell junctions and ion-channels leading to disrupted neuron communication in Parkinson's disease.NPJ Parkinson's disease · 2022Review
- Antagonistic roles of Ras-MAPK and Akt signaling in integrin-KFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues.The Journal of general physiology · 2021Article
- Zinc Signaling in the Mammary Gland: For Better and for Worse.Biomedicines · 2021Review
- [Carbon Monoxide and Pain Regulation: A Review].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Review
- Zinc Increases ABCA1 by Attenuating Its Clearance Through the Modulation of Calmodulin Activity.Journal of atherosclerosis and thrombosis · 2021Article
- Non-Cell-Autonomous Regulation of Optic Nerve Regeneration by Amacrine Cells.Frontiers in cellular neuroscience · 2021Review
- Tyrosine Phosphorylation of the KInternational journal of molecular sciences · 2020Article
- Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.Science advances · 2020Article
- The Redox Biology of Excitotoxic Processes: The NMDA Receptor, TOPA Quinone, and the Oxidative Liberation of Intracellular Zinc.Frontiers in neuroscience · 2020Review
- Excitotoxicity: Still Hammering the Ischemic Brain in 2020.Frontiers in neuroscience · 2020Review
- Voltage-Gated Potassium Channels as Regulators of Cell Death.Frontiers in cell and developmental biology · 2020Review
- A NeurotoxicFrontiers in molecular neuroscience · 2020Review
- Article
- Defining the Kv2.1-syntaxin molecular interaction identifies a first-in-class small molecule neuroprotectant.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
A simultaneous increase in cytosolic Zn(2+) and Ca(2+) accompanies the initiation of neuronal cell death signaling cascades. However, the molecular convergence points of cellular processes activated by these cations are poorly understood. Here, we show that Ca(2+)-dependent activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is required for a cell death-enabling process previously shown to also depend on Zn(2+). We have reported that oxidant-induced intraneuronal Zn(2+) liberation triggers a syntaxin-dependent incorporation of Kv2.1 voltage-gated potassium channels into the plasma membrane. This channel insertion can be detected as a marked enhancement of delayed rectifier K(+) currents in voltage clamp measurements observed at least 3 h following a short exposure to an apoptogenic stimulus. This current increase is the process responsible for the cytoplasmic loss of K(+) that enables protease and nuclease activation during apoptosis. In the present study, we demonstrate that an oxidative stimulus also promotes intracellular Ca(2+) release and activation of CaMKII, which, in turn, modulates the ability of syntaxin to interact with Kv2.1. Pharmacological or molecular inhibition of CaMKII prevents the K(+) current enhancement observed following oxidative injury and, importantly, significantly increases neuronal viability. These findings reveal a previously unrecognized cooperative convergence of Ca(2+)- and Zn(2+)-mediated injurious signaling pathways, providing a potentially unique target for therapeutic intervention in neurodegenerative conditions associated with oxidative stress.
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