ArticleProceedings of the National Academy of Sciences of the United States of America2001
Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 315 citations in OpenAlex.
- Structural determinants at KCNE4 position 145 govern Kv1.3 channel function.The Journal of general physiology · 2026Article
- Potassium suppresses allosteric activation of ZAP-70-dependent T cell receptor signaling.The Journal of biological chemistry · 2026Article
- Ion Channel-Targeting Toxins: Structural Mechanisms of Activation, Inhibition, and Therapeutic Potential.Toxins · 2025Review
- C6 peptide blockade of Hv1 channels inhibits neutrophil migration into the lungs to suppress Pseudomonas aeruginosa-induced acute lung injury.Respiratory research · 2025Article
- Selective inhibition of mitochondrial Kv1.3 prevents and alleviates multiple sclerosis in vivo.EMBO molecular medicine · 2025Article
- Design and synthesis of novel small molecules targeting the Kv1.3 voltage-gated potassium ion channel.Scientific reports · 2025Article
- Platelets as a potential new immune coordinator in T cell-mediated aplastic anemia.Frontiers in oncology · 2025Review
- Polymodal KCommunications biology · 2024Article
- Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with granulomatosis with polyangiitis.Rheumatology (Oxford, England) · 2024Article
- Structure of the voltage-gated potassium channel KChannels (Austin, Tex.) · 2023Review
- Protection from acute lung injury by a peptide designed to inhibit the voltage-gated proton channel.iScience · 2023Article
- A bioengineered probiotic for the oral delivery of a peptide Kv1.3 channel blocker to treat rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neurotoxins and pore forming toxins in sea anemones: Potential candidates for new drug development.Histology and histopathology · 2023Review
- Expression of the ether-a-gò-gò-related gene 1 channel during B and T lymphocyte development: role in BCR and TCR signaling.Frontiers in immunology · 2023Article
- TPC Functions in the Immune System.Handbook of experimental pharmacology · 2023Article
- Modulating the Excitability of Olfactory Output Neurons Affects Whole-Body Metabolism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- How the Potassium Channel Response of T Lymphocytes to the Tumor Microenvironment Shapes Antitumor Immunity.Cancers · 2022Review
- Harnessing the Membrane Potential to Combat Cancer Progression.Bioelectricity · 2022Article
- The voltage-gated potassium channel KV1.3 regulates neutrophil recruitment during inflammation.Cardiovascular research · 2022Article
- Novel insights into the electrophysiology of murine cardiac macrophages: relevance of voltage-gated potassium channels.Cardiovascular research · 2022Article
89 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE), a disease resembling multiple sclerosis, is induced in rats by myelin basic protein (MBP)-activated CD4(+) T lymphocytes. By patch-clamp analysis, encephalitogenic rat T cells stimulated repeatedly in vitro expressed a unique channel phenotype ("chronically activated") with large numbers of Kv1.3 voltage-gated channels (approximately 1500 per cell) and small numbers of IKCa1 Ca(2+)-activated K(+) channels (approximately 50-120 per cell). In contrast, resting T cells displayed 0-10 Kv1.3 and 10-20 IKCa1 channels per cell ("quiescent" phenotype), whereas T cells stimulated once or twice expressed approximately 200 Kv1.3 and approximately 350 IKCa1 channels per cell ("acutely activated" phenotype). Consistent with their channel phenotype, [(3)H]thymidine incorporation by MBP-stimulated chronically activated T cells was suppressed by the peptide ShK, a blocker of Kv1.3 and IKCa1, and by an analog (ShK-Dap(22)) engineered to be highly specific for Kv1.3, but not by a selective IKCa1 blocker (TRAM-34). The combination of ShK-Dap(22) and TRAM-34 enhanced the suppression of MBP-stimulated T cell proliferation. Based on these in vitro results, we assessed the efficacy of K(+) channel blockers in AT-EAE. Specific and simultaneous blockade of the T cell channels by ShK or by a combination of ShK-Dap(22) plus TRAM-34 prevented lethal AT-EAE. Blockade of Kv1.3 alone with ShK-Dap(22), but not of IKCa1 with TRAM-34, was also effective. When administered after the onset of symptoms, ShK or the combination of ShK-Dap(22) plus TRAM-34 greatly ameliorated the clinical course of both moderate and severe AT-EAE. We conclude that selective targeting of Kv1.3, alone or with IKCa1, may provide an effective new mode of therapy for multiple sclerosis.
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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.