ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1435

KCa1.1 Potassium Channels Are a Novel Therapeutic Target on Fibroblast-like Synoviocytes in Rheumatoid Arthritis

Mark Tanner1, Redwan Huq1, Rajeev Tajhya1, Michael Pennington2, Teresina Laragione3, Pércio Gulko4 and Christine Beeton5, 1Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, 2Peptides International, Louisville, KY, 3Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 4Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 5Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Animal models, Fibroblasts, rheumatoid arthritis, synovial fluid, synovium and synovial cells

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Monday, November 14, 2016

Title: Rheumatoid Arthritis – Animal Models - Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Fibroblast-like synoviocytes (FLS) develop a high degree of invasiveness during rheumatoid arthritis (RA), leading to joint degradation. There are currently no therapeutics that specifically target the pathogenic phenotype of FLS. We have previously found that FLS from RA patients and from rats with a model of RA express higher levels of the KCa1.1 potassium channel at their plasma membrane than FLS from patients with osteoarthritis or from healthy rats. Selectively inhibiting KCa1.1 with the small molecule paxilline reduces the in vitro invasiveness of FLS and reduces disease severity in multiple rat models of RA. However, KCa1.1 is expressed in a variety of tissues and systemic KCa1.1 block induces side effects that preclude paxilline’s use as a potential therapeutic in humans. Here, we investigated the efficacy of the peptide KCa1.1 inhibitor iberiotoxin (IbTX), which has a limited biodistribution, in reducing disease severity in an animal model of RA, assessed IbTX’s side effects, and determined the mechanism by which KCa1.1 regulates FLS invasiveness.

Methods:  Starting at disease onset, rats with the pristane-induced arthritis (PIA) model of RA were given either vehicle, paxilline, or IbTX. Disease severity was measured daily using a standard scoring system. After three weeks of treatment, X-rays and histology were completed on paws of rats from each treatment group. Side effects, including incontinence and tremors, were determined in healthy rats given a single treatment of either IbTX, paxilline, or vehicle. Flow cytometry and ex vivo functional assays were used to assess the effects of KCa1.1 inhibition on the expression and activation of signaling molecules involved with FLS invasion.

Results:  Both paxilline and IbTX significantly reduced clinical signs of disease in PIA by approximately 55% (p<0.001) and 65% (p<0.001), respectively, as determined by a standard scoring system of paw inflammation. X-rays and histological analysis of joints from each treatment group indicated that the KCa1.1 blocker-treated rats had less bone and cartilage damage and reduced synovial hyperplasia, fibrosis, and immune infiltrates compared to vehicle-treated animals. Side effects, including tremors and incontinence, were significantly reduced in IbTX-treated rats compared to those treated with paxilline. Ex vivo analysis of RA-FLS demonstrated that KCa1.1 inhibition alters integrin expression and activation through modulation of calcium homeostasis and Akt phosphorylation, resulting in decreased invasiveness.

Conclusion:  KCa1.1 is an attractive therapeutic target for the treatment of RA by inhibiting the invasive phenotype of FLS through modulating integrin expression. The use of the selective peptide KCa1.1 inhibitor IbTX provides for a novel targeted pharmacological approach to inhibit KCa1.1 expressed on FLS while minimizing side effects. Overall, these studies emphasize the efficacy of targeting FLS in reducing disease severity and suggest selective KCa1.1 inhibitors as potential therapeutics in the treatment of RA.


Disclosure: M. Tanner, None; R. Huq, None; R. Tajhya, None; M. Pennington, Peptides International, 1; T. Laragione, None; P. Gulko, None; C. Beeton, None.

To cite this abstract in AMA style:

Tanner M, Huq R, Tajhya R, Pennington M, Laragione T, Gulko P, Beeton C. KCa1.1 Potassium Channels Are a Novel Therapeutic Target on Fibroblast-like Synoviocytes in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/kca1-1-potassium-channels-are-a-novel-therapeutic-target-on-fibroblast-like-synoviocytes-in-rheumatoid-arthritis/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/kca1-1-potassium-channels-are-a-novel-therapeutic-target-on-fibroblast-like-synoviocytes-in-rheumatoid-arthritis/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology