ArticleJournal of neuroinflammation2017
A systems pharmacology-based approach to identify novel Kv1.3 channel-dependent mechanisms in microglial activation.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 86 citations in OpenAlex.
- Ventromedial hypothalamus IL-6 signaling mediates the excessive aggressive behavior induced by late-gestational sleep deprivation in male mice.Behavioral and brain functions : BBF · 2026Article
- SARS-CoV-2 Spike Protein S1 Subunit Induces Neuroinflammation Via Microglial Kv1.3 Channel.Biological psychiatry global open science · 2026Article
- Kv1.3 as an upstream regulator of oxidative stress-mediated neuroinflammation following organic dust exposure in murineFrontiers in toxicology · 2026Article
- High-Throughput Label-free Single-Cell Proteomics Enabled by Multicolumn NanoLC with a 5-min Cycle Time.Research square · 2025Article
- Chlorpromazine directly inhibits Kv1.3 channels by facilitating the inactivation of channels.Molecular brain · 2025Article
- ShK-modified UCMSCs Inhibit M1-Like Macrophage Polarization and Alleviate Osteoarthritis Progression via PI3K/Akt Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Identification of State-Specific Proteomic and Transcriptomic Signatures of Microglia-Derived Extracellular Vesicles.Molecular & cellular proteomics : MCP · 2023Article
- Shear-induced phenotypic transformation of microglia in vitro.Biophysical journal · 2023Article
- Functional Potassium Channels in Macrophages.The Journal of membrane biology · 2023Review
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- Non-conducting functions of potassium channels in cancer and neurological disease.Current topics in membranes · 2023Review
- Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions.Journal of neuroinflammation · 2022Article
- Microglial ion channels: Key players in non-cell autonomous neurodegeneration.Neurobiology of disease · 2022Review
- BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia.Molecular neurodegeneration · 2022Article
- Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology.Brain sciences · 2022Review
- Dlg1 Knockout Inhibits Microglial Activation and Alleviates Lipopolysaccharide-Induced Depression-Like Behavior in Mice.Neuroscience bulletin · 2021Article
- Kv1.3 inhibition attenuates neuroinflammation through disruption of microglial calcium signaling.Channels (Austin, Tex.) · 2021Review
- Unique molecular characteristics and microglial origin of Kv1.3 channel-positive brain myeloid cells in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration.International journal of molecular sciences · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundKv1.3 potassium channels regulate microglial functions and are overexpressed in neuroinflammatory diseases. Kv1.3 blockade may selectively inhibit pro-inflammatory microglia in neurological diseases but the molecular and cellular mechanisms regulated by Kv1.3 channels are poorly defined.
methodsWe performed immunoblotting and flow cytometry to confirm Kv1.3 channel upregulation in lipopolysaccharide (LPS)-activated BV2 microglia and in brain mononuclear phagocytes freshly isolated from LPS-treated mice. Quantitative proteomics was performed on BV2 microglia treated with control, LPS, ShK-223 (highly selective Kv1.3 blocker), and LPS+ShK-223. Gene ontology (GO) analyses of Kv1.3-dependent LPS-regulated proteins were performed, and the most representative proteins and GO terms were validated. Effects of Kv1.3-blockade on LPS-activated BV2 microglia were studied in migration, focal adhesion formation, reactive oxygen species production, and phagocytosis assays. In vivo validation of protein changes and predicted molecular pathways were performed in a model of systemic LPS-induced neuroinflammation, employing antigen presentation and T cell proliferation assays. Informed by pathway analyses of proteomic data, additional mechanistic experiments were performed to identify early Kv1.3-dependent signaling and transcriptional events.
resultsLPS-upregulated cell surface Kv1.3 channels in BV2 microglia and in microglia and CNS-infiltrating macrophages isolated from LPS-treated mice. Of 144 proteins differentially regulated by LPS (of 3141 proteins), 21 proteins showed rectification by ShK-223. Enriched cellular processes included MHCI-mediated antigen presentation (TAP1, EHD1), cell motility, and focal adhesion formation. In vitro, ShK-223 decreased LPS-induced focal adhesion formation, reversed LPS-induced inhibition of migration, and inhibited LPS-induced upregulation of EHD1, a protein involved in MHCI trafficking. In vivo, intra-peritoneal ShK-223 inhibited LPS-induced MHCI expression by CD11b
conclusionsWe have unraveled novel molecular and functional roles for Kv1.3 channels in pro-inflammatory microglial activation, including a Kv1.3 channel-regulated pathway that facilitates MHCI expression and MHCI-dependent antigen presentation by microglia to CD8
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