ArticleNature immunology2012
A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells.
Article in Nature immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed.
- Neosaxitoxin Downregulates Inflammation in an Equine In Vivo Model of Osteoarthritis.Biomolecules · 2026Article
- Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.Nature immunology · 2025Article
- Sodium channels in non-excitable cells: powerful actions and therapeutic targets beyond Hodgkin and Huxley.Trends in cell biology · 2025Review
- The partitioning of TCR repertoires by thymic selection.The Journal of experimental medicine · 2024Review
- Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development.The Journal of experimental medicine · 2024Review
- Is the regulation of lamotrigine on depression in patients with epilepsy related to cytokines?Heliyon · 2024Article
- Genomic view of the origins of cell-mediated immunity.Immunogenetics · 2023Article
- SCN4B inhibits the progression of lung adenocarcinoma and is associated with better prognosis.The clinical respiratory journal · 2023Article
- Review
- Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain.Brain sciences · 2023Article
- Frontline Sodium Channel-Blocking Antiseizure Medicine Use Promotes Future Onset of Drug-Resistant Chronic Seizures.International journal of molecular sciences · 2023Article
- Voltage-gated sodium channels: from roles and mechanisms in the metastatic cell behavior to clinical potential as therapeutic targets.Frontiers in pharmacology · 2023Review
- Antitumor effects and potential mechanisms of aconitine based on preclinical studies: an updated systematic review and meta-analysis.Frontiers in pharmacology · 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
- The perception and response of T cells to a changing environment are based on the law of initial value.Science signaling · 2022Review
- Non-canonical endogenous expression of voltage-gated sodium channel NaThe Journal of physiology · 2022Article
- Article
- A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.Purinergic signalling · 2022Review
- Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives.Biomolecules · 2022Review
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
10 more citing papers are in PubMed but not listed here.
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3 authors.
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Abstract
The sustained entry of Ca(2+) into CD4(+)CD8(+) double-positive thymocytes is required for positive selection. Here we identified a voltage-gated Na(+) channel (VGSC) that was essential for positive selection of CD4(+) T cells. Pharmacological inhibition of VGSC activity inhibited the sustained Ca(2+) influx induced by positively selecting ligands and the in vitro positive selection of CD4(+) but not CD8(+) T cells. In vivo short hairpin RNA (shRNA)-mediated knockdown of the gene encoding a regulatory β-subunit of a VGSC specifically inhibited the positive selection of CD4(+) T cells. Ectopic expression of VGSC in peripheral AND CD4(+) T cells bestowed the ability to respond to a positively selecting ligand, which directly demonstrated that VGSC expression was responsible for the enhanced sensitivity. Thus, active VGSCs in thymocytes provide a mechanism by which a weak positive selection signal can induce the sustained Ca(2+) signals required for CD4(+) T cell development.
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