KCa1.1 channels regulate {beta}1 integrin function and cell adhesion in rheumatoid arthritis fibroblast-like synoviocytes [Research]

Large-conductance calcium-activated potassium channel (KCa1.1; BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of fibroblast-like synoviocytes isolated from the synovium of patients with rheumatoid arthritis (RA-FLS). 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 β₁ integrins, but not α₄, α₅, or α₆ integrins. Blocking KCa1.1 disturbs calcium homeostasis, leading to the sustained phosphorylation of Akt and the recruitment of talin to β₁ integrins. Interestingly, the pore-forming α subunit of KCa1.1 coimmunoprecipitates with β₁ 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 β₁ integrin function and therefore invasiveness of RA-FLS.—Tanner, M. R., Pennington, M. W., Laragione, T., Gulko, P. S., Beeton, C. KCa1.1 channels regulate β₁ integrin function and cell adhesion in rheumatoid arthritis fibroblast-like synoviocytes.

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