title: Endothelial progenitor cells functionally express inward rectifier potassium channels.
abstract: Since the first isolation of endothelial progenitor cells (EPCs) from human peripheral blood in 1997, many researchers have conducted studies to understand the characteristics and therapeutic effects of EPCs in vascular disease models. Nevertheless, the electrophysiological properties of EPCs have yet to be clearly elucidated. The inward rectifier potassium channel (Kir) performs a major role in controlling the membrane potential and cellular events. Here, via the whole cell patch-clamp technique, we found inwardly rectifying currents in EPCs and that these currents were inhibited by Ba(2+) (100 μM) and Cs(+) (1 mM), known as Kir blockers, in a dose-dependent manner (Ba(2+), 91.2 ± 1.4% at -140 mV and Cs(+), 76.1 ± 6.9% at -140 mV, respectively). Next, using DiBAC(3), a fluorescence indicator of membrane potential, we verified that Ba(2+) induced an increase of fluorescence in EPCs (10 μM, 123 ± 2.8%), implying the depolarization of EPCs. At the mRNA and protein levels, we confirmed the existence of several Kir subtypes, including Kir2.x, 3.x, 4.x, and 6.x. In a functional experiment, we observed that, in the presence of Ba(2+), the number of tubes on Matrigel formed by EPCs was dose-dependently reduced (10 μM, 62.3 ± 6.5%). In addition, the proliferation of EPCs was increased in a dose-dependent fashion (10 μM, 157.9 ± 17.4%), and specific inhibition of Kir2.1 by small interfering RNA also increased the proliferation of EPCs (116.2 ± 2.5%). Our results demonstrate that EPCs express several types of Kir which may modulate the endothelial function and proliferation of EPCs.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Jang
authors.forename: Jonghanne
authors.initials: J
authors.lastname: Park
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Hur
authors.forename: Yun Hwa
authors.initials: YH
authors.lastname: Hong
authors.forename: Jin
authors.initials: J
authors.lastname: Hur
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chae
authors.forename: Seung Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Jun
authors.initials: J
authors.lastname: Kim
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Sang Jeong
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D001464:Barium / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation; D002586:Cesium / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D005312:Fetal Blood; D005455:Fluorescent Antibody Technique; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D013234:Stem Cells / Q000378:metabolism*
chemical_list: C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D034741:RNA, Small Interfering; D002586:Cesium; D001464:Barium; D011188:Potassium