KCa1.1 potassium channels regulate key proinflammatory and invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis

J Biol Chem. 2012 Feb 3;287(6):4014-22. doi: 10.1074/jbc.M111.312264. Epub 2011 Nov 10.

Abstract

Fibroblast-like synoviocytes (FLS) play important roles in the pathogenesis of rheumatoid arthritis (RA). Potassium channels have regulatory roles in many cell functions. We have identified the calcium- and voltage-gated KCa1.1 channel (BK, Maxi-K, Slo1, KCNMA1) as the major potassium channel expressed at the plasma membrane of FLS isolated from patients with RA (RA-FLS). We further show that blocking this channel perturbs the calcium homeostasis of the cells and inhibits the proliferation, production of VEGF, IL-8, and pro-MMP-2, and migration and invasion of RA-FLS. Our findings indicate a regulatory role of KCa1.1 channels in RA-FLS function and suggest this channel as a potential target for the treatment of RA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Calcium / metabolism
  • Cell Membrane / metabolism*
  • Cell Membrane / pathology
  • Cell Proliferation
  • Enzyme Precursors / biosynthesis
  • Female
  • Gelatinases / biosynthesis
  • Gene Expression Regulation*
  • HEK293 Cells
  • Homeostasis
  • Humans
  • Interleukin-8 / biosynthesis
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / antagonists & inhibitors
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / biosynthesis*
  • Male
  • Middle Aged
  • Rheumatic Fever / metabolism*
  • Rheumatic Fever / pathology
  • Synovial Fluid / metabolism*
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • CXCL8 protein, human
  • Enzyme Precursors
  • Interleukin-8
  • KCNMA1 protein, human
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Gelatinases
  • progelatinase
  • Calcium