ArticleArthritis research & therapy2016
Different expression of β subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Two-pore domain potassium channel TREK-1 contributes to arachidonic acid-induced CaBiochemistry and biophysics reports · 2025Article
- Exploring the therapeutic opportunities of potassium channels for the treatment of rheumatoid arthritis.Frontiers in pharmacology · 2024Review
- Single-cell RNA sequencing in osteoarthritis.Cell proliferation · 2023Review
- CaInternational journal of molecular sciences · 2023Review
- Antioxidant Carbon Nanoparticles Inhibit Fibroblast-Like Synoviocyte Invasiveness and Reduce Disease Severity in a Rat Model of Rheumatoid Arthritis.Antioxidants (Basel, Switzerland) · 2020Article
- Pro-inflammatory Cytokines Drive Deregulation of Potassium Channel Expression in Primary Synovial Fibroblasts.Frontiers in physiology · 2020Article
- Regulation of BK Channels by Beta and Gamma Subunits.Annual review of physiology · 2019Review
- KCa1.1 and Kv1.3 channels regulate the interactions between fibroblast-like synoviocytes and T lymphocytes during rheumatoid arthritis.Arthritis research & therapy · 2019Article
- Targeting KCa1.1 Channels with a Scorpion Venom Peptide for the Therapy of Rat Models of Rheumatoid Arthritis.The Journal of pharmacology and experimental therapeutics · 2018Article
- Differences in ion channel phenotype and function between humans and animal models.Frontiers in bioscience (Landmark edition) · 2018Review
- KCa1.1 channels as therapeutic targets for rheumatoid arthritis.Expert opinion on therapeutic targets · 2017Article
- MicroRNA-192 suppresses cell proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes by downregulating caveolin 1.Molecular and cellular biochemistry · 2017Article
- KCa1.1 channels regulate βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog.Clinical immunology (Orlando, Fla.) · 2017Article
- Functional KCa1.1 channels are crucial for regulating the proliferation, migration and differentiation of human primary skeletal myoblasts.Cell death & disease · 2016Article
- Erratum to: Different expression of β subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes.Arthritis research & therapy · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundFibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA-FLS) contribute to joint inflammation and damage characteristic of the disease. RA-FLS express KCa1.1 (BK, Slo1, MaxiK, KCNMA1) as their major plasma membrane potassium channel. Blocking KCa1.1 reduces the invasive phenotype of RA-FLS and attenuates disease severity in animal models of RA. This channel has therefore emerged as a promising therapeutic target in RA. However, the pore-forming α subunit of KCa1.1 is widely distributed in the body, and blocking it induces severe side effects, thus limiting its value as a therapeutic target. On the other hand, KCa1.1 channels can also contain different accessory subunits with restricted tissue distribution that regulate channel kinetics and pharmacology. Identification of the regulatory subunits of KCa1.1 expressed by RA-FLS may therefore provide the opportunity for generating a selective target for RA treatment.
methodsHighly invasive RA-FLS were isolated from patients with RA, and FLS from patients with osteoarthritis (OA) were used as minimally invasive controls. The β subunit expression by FLS was assessed by quantitative reverse transcription polymerase chain reactions, Western blotting, and patch-clamp electrophysiology combined with pharmacological agents. FLS were sorted by flow cytometry on the basis of their CD44 expression level for comparison of their invasiveness and with their expression of KCa1.1 α and β subunits. β1 and β3 subunit expression was reduced with small interfering RNA (siRNA) to assess their specific role in KCa1.1α expression and function and in FLS invasiveness.
resultsWe identified functional β1 and β3b regulatory subunits in RA-FLS. KCa1.1 β3b subunits were expressed by 70 % of the cells and were associated with highly invasive CD44(high) RA-FLS, whereas minimally invasive CD44(low) RA-FLS and OA-FLS expressed either β1 subunit. Furthermore, we found that silencing the β3 but not the β1 subunit with siRNA reduced KCa1.1 channel density at the plasma membrane of RA-FLS and inhibited RA-FLS invasiveness.
conclusionsOur findings suggest the KCa1.1 channel composed of α and β3b subunits as an attractive target for the therapy of RA.
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