The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Kir4.1 is coexpressed with stemness markers in activated astrocytes in the injured brain and a Kir4.1 inhibitor BaCl2 negatively regulates neurosphere formation in culture

  • Kwon, Jae-Kyung (Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine) ;
  • Choi, Dong-Joo (Department of Pharmacology, Ajou University School of Medicine) ;
  • Yang, Haijie (Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine) ;
  • Ko, Dong Wan (Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine) ;
  • Jou, Ilo (Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine) ;
  • Park, Sang Myun (Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine) ;
  • Joe, Eun-Hye (Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine)
  • Received : 2021.05.09
  • Accepted : 2021.09.07
  • Published : 2021.11.01
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Abstract

Astrocytes are activated in response to brain damage. Here, we found that expression of Kir4.1, a major potassium channel in astrocytes, is increased in activated astrocytes in the injured brain together with upregulation of the neural stem cell markers, Sox2 and Nestin. Expression of Kir4.1 was also increased together with that of Nestin and Sox2 in neurospheres formed from dissociated P7 mouse brains. Using the Kir4.1 blocker BaCl2 to determine whether Kir4.1 is involved in acquisition of stemness, we found that inhibition of Kir4.1 activity caused a concentration-dependent increase in sphere size and Sox2 levels, but had little effect on Nestin levels. Moreover, induction of differentiation of cultured neural stem cells by withdrawing epidermal growth factor and fibroblast growth factor from the culture medium caused a sharp initial increase in Kir4.1 expression followed by a decrease, whereas Sox2 and Nestin levels continuously decreased. Inhibition of Kir4.1 had no effect on expression levels of Sox2 or Nestin, or the astrocyte and neuron markers glial fibrillary acidic protein and β-tubulin III, respectively. Taken together, these results indicate that Kir4.1 may control gain of stemness but not differentiation of stem cells.

Keywords

Acknowledgement

This work was supported by grants funded by the Korean government (NRF-2017R1A2B3011281 and NRF-2016M3C7A1905072), and a grant from KOSEF through the Chronic Inflammatory Disease Research Center at Ajou University (NRF-2012R1A5A048183) to EJ.

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