title: Effects of BKCa and Kir2.1 Channels on Cell Cycling Progression and Migration in Human Cardiac c-kit+ Progenitor Cells.
abstract: Our previous study demonstrated that a large-conductance Ca2+-activated K+ current (BKCa), a voltage-gated TTX-sensitive sodium current (INa.TTX), and an inward rectifier K+ current (IKir) were heterogeneously present in most of human cardiac c-kit+ progenitor cells. The present study was designed to investigate the effects of these ion channels on cell cycling progression and migration of human cardiac c-kit+ progenitor cells with approaches of cell proliferation and mobility assays, siRNA, RT-PCR, Western blots, flow cytometry analysis, etc. It was found that inhibition of BKCa with paxilline, but not INa.TTX with tetrodotoxin, decreased both cell proliferation and migration. Inhibition of IKir with Ba2+ had no effect on cell proliferation, while enhanced cell mobility. Silencing KCa.1.1 reduced cell proliferation by accumulating the cells at G0/G1 phase and decreased cell mobility. Interestingly, silencing Kir2.1 increased the cell migration without affecting cell cycling progression. These results demonstrate the novel information that blockade or silence of BKCa channels, but not INa.TTX channels, decreases cell cycling progression and mobility, whereas inhibition of Kir2.1 channels increases cell mobility without affecting cell cycling progression in human cardiac c-kit+ progenitor cells.
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China; Xiamen Cardiovascular Hospital, Medical School of Xiamen University, Xiamen, Fujian, 361004, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Che
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Xiamen Cardiovascular Hospital, Medical School of Xiamen University, Xiamen, Fujian, 361004, China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Xiao
authors.affiliation: Xiamen Cardiovascular Hospital, Medical School of Xiamen University, Xiamen, Fujian, 361004, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China; Xiamen Cardiovascular Hospital, Medical School of Xiamen University, Xiamen, Fujian, 361004, China.
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
mesh_terms: D001464:Barium / Q000494:pharmacology; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: D007211:Indoles; C489457:KCNJ2 protein, human; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D001464:Barium; C048220:paxilline; D019009:Proto-Oncogene Proteins c-kit