Targeting Potassium Channels On Fibroblast‐like Synoviocytes For The Treatment Of Pristane Induced Arthritis In A Rat Model

Abstract

Targeting Potassium Channels On Fibroblast‐like Synoviocytes For The Treatment Of Pristane Induced Arthritis In A Rat Model Rheumatoid arthritis (RA) is a chronic disease that leads to inflammation of the joints and other organs. Fibroblast‐like synoviocytes (FLS) play an important role in the pathogenesis of RA. We have previously identified and defined the roles of the major functional K+ channels KCa1.1 channels (BK, Maxi‐K, slo1) expressed at the plasma membrane of FLS isolated from patients with RA (RA‐FLS). In the present study, we used RT‐PCR, western blotting, immunocytochemistry, and patch‐clamp electrophysiology to identify KCa1.1 channels as the major functional K+ channels expressed by FLS isolated from rats with pristane‐induced arthritis (PIA), an animal model for RA. Blocking KCa1.1 channels inhibited the proliferation of these cells and their ability to produce MMP‐2 without inducing cytotoxicity. In keeping with these results, blocking KCa1.1 channels also inhibited the invasion of RA‐FLS in Matrigel assays. Furthermore, a KCa1.1 blocker, injected every other day after onset of PIA clinical signs, stopped disease progression. Our findings demonstrated that KCa1.1 channels on fibroblast‐like synoviocytes are promising therapeutic targets for the treatment of RA.This study is supported by funding from Baylor College of Medicine and the NIH (AI084981).