title: Functional KCa3.1 K+ channels are required for human fibrocyte migration.
abstract: BACKGROUND
  Fibrocytes are bone marrow-derived CD34(+) collagen I-positive cells present in peripheral blood that develop α-smooth muscle actin expression and contractile activity in tissue culture. They are implicated in the pathogenesis of tissue remodeling and fibrosis in both patients with asthma and those with idiopathic pulmonary fibrosis. Targeting fibrocyte migration might therefore offer a new approach for the treatment of these diseases. Ion channels play key roles in cell function, but the ion-channel repertoire of human fibrocytes is unknown.
  
  
  OBJECTIVE
  We sought to examine whether human fibrocytes express the K(Ca)3.1 K(+) channel and to determine its role in cell differentiation, survival, and migration.
  
  
  METHODS
  Fibrocytes were cultured from the peripheral blood of healthy subjects and patients with asthma. Whole-cell patch-clamp electrophysiology was used for the measurement of ion currents, whereas mRNA and protein were examined to confirm channel expression. Fibrocyte migration and proliferation assays were performed in the presence of K(Ca)3.1 ion-channel blockers.
  
  
  RESULTS
  Human fibrocytes cultured from the peripheral blood of both healthy control subjects and asthmatic patients expressed robust K(Ca)3.1 ion currents together with K(Ca)3.1 mRNA and protein. Two specific and distinct K(Ca)3.1 blockers (TRAM-34 and ICA-17043) markedly inhibited fibrocyte migration in transwell migration assays. Channel blockers had no effect on fibrocyte growth, apoptosis, or differentiation in cell culture.
  
  
  CONCLUSIONS
  The K(+) channel K(Ca)3.1 plays a key role in human fibrocyte migration. Currently available K(Ca)3.1-channel blockers might therefore attenuate tissue fibrosis and remodeling in patients with diseases such as idiopathic pulmonary fibrosis and asthma through the inhibition of fibrocyte recruitment.
authors.affiliation: Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
authors.forename: Glenn
authors.initials: G
authors.lastname: Cruse
authors.forename: Shailendra R
authors.initials: SR
authors.lastname: Singh
authors.forename: S Mark
authors.initials: SM
authors.lastname: Duffy
authors.forename: Camille
authors.initials: C
authors.lastname: Doe
authors.forename: Ruth
authors.initials: R
authors.lastname: Saunders
authors.forename: Chris E
authors.initials: CE
authors.lastname: Brightling
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
mesh_terms: D056151:Airway Remodeling / Q000502:physiology; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement; D003239:Connective Tissue Cells / Q000166:cytology* / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human