KCa1.1 channels regulate b1-integrin function and cell adhesion in rheumatoid arthritis fibroblast-like synoviocytes

Abstract

Large-conductance calcium-activated potassium channel (KCa1.1; BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) isolated from the synovium of patients with RA. It is a critical regulator of RA-FLS migration and invasion and therefore represents an attractive target for the therapy of RA. However, the molecular mechanisms by which KCa1.1 regulates RA-FLS invasiveness have remained largely unknown. Here, we demonstrate that KCa1.1 regulates RA-FLS adhesion through controlling the plasma membrane expression and activation of b1 integrins, but not a4, a5, or a6 integrins. Blocking KCa1.1 disturbs calcium homeostasis, leading to the sustained phosphorylation of Akt and the recruitment of talin to b1 integrins. Interestingly, the pore-forming a subunit of KCa1.1 coimmunoprecipitates with b1 integrins, suggesting that this physical association underlies the functional interaction between these molecules. Together, these data outline a new signaling mechanism by which KCa1.1 regulates b1-integrin function and therefore invasiveness of RA-FLSs.—Tanner, M. R., Pennington, M. W., Laragione, T., Gulko, P. S., Beeton, C. KCa1.1 channels regulate b1-integrin function and cell adhesion in rheumatoid arthritis fibroblast-like synoviocytes.