title: KCa1.1 potassium channels regulate key proinflammatory and invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis.
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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Xueyou
authors.initials: X
authors.lastname: Hu
authors.forename: Teresina
authors.initials: T
authors.lastname: Laragione
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.forename: Shyny
authors.initials: S
authors.lastname: Koshy
authors.forename: Karlie R
authors.initials: KR
authors.lastname: Jones
authors.forename: Iskander I
authors.initials: II
authors.lastname: Ismailov
authors.forename: Patricia
authors.initials: P
authors.lastname: Yotnda
authors.forename: Frank T
authors.initials: FT
authors.lastname: Horrigan
authors.forename: Pércio S
authors.initials: PS
authors.lastname: Gulko
authors.forename: Christine
authors.initials: C
authors.lastname: Beeton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D004792:Enzyme Precursors / Q000096:biosynthesis; D005260:Female; D018093:Gelatinases / Q000096:biosynthesis; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D012213:Rheumatic Fever / Q000378:metabolism* / Q000473:pathology; D013582:Synovial Fluid / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C508606:CXCL8 protein, human; D004792:Enzyme Precursors; D016209:Interleukin-8; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D018093:Gelatinases; C069860:progelatinase; D002118:Calcium
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