ArticleProceedings of the National Academy of Sciences of the United States of America2006
Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 283 papers.
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Who cites it
283 citing papers in PubMed.
- Trial
- KArchiv der Pharmazie · 2026Article
- Nanobody regulation of C-type inactivation in Kv1.3 channels.Nature communications · 2026Article
- Structural determinants at KCNE4 position 145 govern Kv1.3 channel function.The Journal of general physiology · 2026Article
- Challenges in tracer development for tumor microenvironment (TME) imaging.European journal of nuclear medicine and molecular imaging · 2026Review
- Integrated Screening Cascades for Ion-Channel Drug Discovery: Linking Structure, Electrophysiology, Safety Pharmacology, and Human-Relevant Models.International journal of molecular sciences · 2026Review
- Potassium suppresses allosteric activation of ZAP-70-dependent T cell receptor signaling.The Journal of biological chemistry · 2026Article
- Kv1.3 palmitoylation regulates spatial distribution and channel removal from the immunological synapse.Cellular and molecular life sciences : CMLS · 2026Article
- Kv1.3 Channel inhibition by nanoformulated MeuKTx as a therapeutic strategy in breast cancer.Scientific reports · 2026Article
- Kv1.3 regulates macrophage immune function through PI3K/AKT signaling pathway to alleviate metabolic dysfunction-associated steatohepatitis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Article
- Voltage-dependent potassium channel regulatory subunits in the immune system.Biophysical reviews · 2026Review
- From venom peptides to neurotherapeutics: BmK defensins and short-chain peptides as modulators of ion channels.Frontiers in pharmacology · 2026Review
- Targeting mitochondrial Kv1.3 enables precise autoreactive T cell therapy for multiple sclerosis.EMBO molecular medicine · 2025Article
- Recent advances in the pharmacology of voltage-gated ion channels.Pharmacological reviews · 2025Review
- Selective inhibition of mitochondrial Kv1.3 prevents and alleviates multiple sclerosis in vivo.EMBO molecular medicine · 2025Article
- Identification of Novel Kv1.3 Channel-Interacting Proteins Using Proximity Labelling in T-Cells.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2025Article
- Properties and Pharmacology of Scorpion Toxins and Their Biotechnological Potential in Agriculture and Medicine.Toxins · 2025Review
- Molecular determinants for the endocytosis of the voltage-gated KScience signaling · 2025Article
- Design and synthesis of novel small molecules targeting the Kv1.3 voltage-gated potassium ion channel.Scientific reports · 2025Article
223 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors.
Funding
Abstract
Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression. In contrast, T cells with other antigen specificities from these patients, or autoreactive T cells from healthy individuals and disease controls, express low levels of Kv1.3 and are predominantly naïve or central-memory (T(CM)) cells. In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4. Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells. Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats. Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted.
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