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

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.