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Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis

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Abstract

Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS). In the present study we investigated temporal and cellular expression pattern of this channel in the lumbar part of spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), animal model of MS. EAE was actively induced in female Dark Agouti rats. Expression of Kv1.3 was analyzed at different time points of disease progression, at the onset, peak and end of EAE. We here show that Kv1.3 increased by several folds at the peak of EAE at both gene and protein level. Double immunofluorescence analyses demonstrated localization of Kv1.3 on activated microglia, macrophages, and reactive astrocytes around inflammatory lesions. In vitro experiments showed that pharmacological block of Kv1.3 in activated astrocytes suppresses the expression of proinflammatory mediators, suggesting a role of this channel in inflammation. Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.

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Acknowledgements

Some data sets included in this manuscript were presented as an abstract at the 4th Meeting of COST Action BM1406: Ion Channels and Immune Response toward a global understanding of immune cell physiology and for new therapeutic approaches (IONCHAN-IMMUNRESPON).

Funding

This work was funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Grant III 41014.

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Authors and Affiliations

  1. Department of Neurobiology, Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Blvd Despota Stefana 142, 11060, Belgrade, Serbia

    Iva Bozic, Katarina Tesovic, Marija Jakovljevic, Ivana Bjelobaba, Danijela Savic, Sanja Pekovic & Irena Lavrnja

  2. Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia

    Danijela Laketa, Marija Adzic & Nadezda Nedeljkovic

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  1. Iva Bozic
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All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of Ethical Committee for the Use of Laboratory Animals of Institute for Biological Research “Sinisa Stankovic” (Belgrade, Serbia), in compliance with EEC Directive (2010/63/EU) on the protection of animals used for experimental and other scientific purposes.

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Bozic, I., Tesovic, K., Laketa, D. et al. Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis. Neurochem Res 43, 1020–1034 (2018). https://doi.org/10.1007/s11064-018-2509-8

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