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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

The potassium channel KCa3.1 constitutes a pharmacological target for astrogliosis associated with ischemia stroke

Authors: Mengni Yi, Tianjiao Wei, Yanxia Wang, Qin Lu, Gaoxian Chen, Xiaoling Gao, Herbert M. Geller, Hongzhuan Chen, Zhihua Yu

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Reactive astrogliosis is one of the significantly pathological features in ischemic stroke accompanied with changes in gene expression, morphology, and proliferation. KCa3.1 was involved in TGF-β-induced astrogliosis in vitro and also contributed to astrogliosis-mediated neuroinflammation in neurodegeneration disease.

Methods

Wild type mice and KCa3.1−/− mice were subjected to permanent middle cerebral artery occlusion (pMCAO) to evaluate the infarct areas by 2,3,5-triphenyltetrazolium hydrochloride staining and neurological deficit. KCa3.1 channels expression and cell localization in the brain of pMCAO mice model were measured by immunoblotting and immunostaining. Glia activation and neuron loss was measured by immunostaining. DiBAC4 (3) and Fluo-4AM were used to measure membrane potential and cytosolic Ca2+ level in oxygen-glucose deprivation induced reactive astrocytes in vitro.

Results

Immunohistochemistry on pMCAO mice infarcts showed strong upregulation of KCa3.1 immunoreactivity in reactive astrogliosis. KCa3.1−/− mice exhibited significantly smaller infarct areas on pMCAO and improved neurological deficit. Both activated gliosis and neuronal loss were attenuated in KCa3.1−/− pMCAO mice. In the primary cultured astrocytes, the expressions of KCa3.1 and TRPV4 were increased associated with upregulation of astrogliosis marker GFAP induced by oxygen-glucose deprivation. The activation of KCa3.1 hyperpolarized membrane potential and, by promoting the driving force for calcium, induced calcium entry through TRPV4, a cation channel of the transient receptor potential family. Double-labeled staining showed that KCa3.1 and TRPV4 channels co-localized in astrocytes. Blockade of KCa3.1 or TRPV4 inhibited the phenotype switch of reactive astrogliosis.

Conclusions

Our data suggested that KCa3.1 inhibition might represent a promising therapeutic strategy for ischemia stroke.
Appendix
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Metadata
Title
The potassium channel KCa3.1 constitutes a pharmacological target for astrogliosis associated with ischemia stroke
Authors
Mengni Yi
Tianjiao Wei
Yanxia Wang
Qin Lu
Gaoxian Chen
Xiaoling Gao
Herbert M. Geller
Hongzhuan Chen
Zhihua Yu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0973-8

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