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

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.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Bozic I,Tesovic K,Laketa D,Adzic M,Jakovljevic M,Bjelobaba I,Savic D,Nedeljkovic N,Pekovic S,Lavrnja I

doi

10.1007/s11064-018-2509-8

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

1020-1034

issue

5

eissn

0364-3190

issn

1573-6903

pii

10.1007/s11064-018-2509-8

journal_volume

43

pub_type

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