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Effects of Ca2+-activated potassium and inward rectifier potassium channel on the differentiation of endothelial progenitor cells from human peripheral blood

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Abstract

Endothelial progenitor cells (EPCs) are bone marrow-derived cells that have the propensity to differentiate into mature endothelial cells (ECs). The transplantation of EPCs has been shown to enhance in vivo postnatal neo-vasculogenesis, as well as repair infarcted myocardium. Via the whole-cell patch clamp technique, numerous types of ion channels have been detected in EPCs, including the inward rectifier potassium channel (IKir), Ca2+-activated potassium channel (IKCa), and volume-sensitive chloride channel, but their influence on the differentiation of EPCs has yet to be characterized. The present study was designed to investigate: (1) which ion channels have the most significant impact on the differentiation of EPCs; (2) what role ion channels play in the functional development of EPCs; (3) the mRNA and protein expression levels of related ion channel subunits in EPCs. In our study, EPCs were obtained from the peripheral blood of healthy adults and cultured with endothelial growth factors. When EPCs differentiate into mature ECs, they lose expression of the stem cell/progenitor marker CD133, as analyzed by flow cytometry (0.44 ± 0.20 %). However, treatment with the potassium channel inhibitor, tetraethylammonium (TEA) results in an increase in CD133+ cells (25.50 ± 7.55 %). In a functional experiment, we observed a reduction in the capacity of TEA treated ECs (differentiated from EPCs) to form capillary tubes when seeded in Matrigel. At the mRNA and protein levels, we revealed several K+ subtypes, including KCNN4 for IKCa, KCNNMA1 for BKCa and Kir3.4 for IKir. These results demonstrate for the first time that potassium channels play a significant role in the differentiation of EPCs. Moreover, inhibition of potassium channels may depress the differentiation of EPCs and the significant potassium channel subunits in EPCs appear to be IKCa, BKCa and Kir3.4.

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Acknowledgment

This research was supported by the following Grants: Advanced Key Scientific and Technological Programs of NingBo (2011C5100), Fund of NingBo Science and Technology Innovation Team (2011B82015), National natural Science Foundation of NingBo (2010A610035), Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents, The Project of NingBo Medicine and Science (2009A01).

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Authors and Affiliations

  1. LiHuiLi Hospital, Medical School of NingBo University, Ningbo, 3154041, People’s Republic of China

    Gongjie Ye, Haiwang Guan, Feng Wang, Xiaoyong Xu, Haiyan Mao, Xiaoyan Huang, Xi Yang, Ping Peng, Yanna Ba, Jianqing Zhou & Jiangfang Lian

  2. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Justin Karush

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  1. Gongjie Ye
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  2. Haiwang Guan
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Correspondence to Justin Karush.

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Gongjie Ye, Haiwang Guan and Justin Karush contributed equally to this work.

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Ye, G., Guan, H., Karush, J. et al. Effects of Ca2+-activated potassium and inward rectifier potassium channel on the differentiation of endothelial progenitor cells from human peripheral blood. Mol Biol Rep 41, 3413–3423 (2014). https://doi.org/10.1007/s11033-014-3203-9

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