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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2020

Open Access 01-12-2020 | Research

The impact of hyperpolarization-activated cyclic nucleotide-gated (HCN) and voltage-gated potassium KCNQ/Kv7 channels on primary microglia function

Authors: Sabine Ulrike Vay, Lea Jessica Flitsch, Monika Rabenstein, Helena Monière, Igor Jakovcevski, Pavle Andjus, Dunja Bijelic, Stefan Blaschke, Helene Luise Walter, Gereon Rudolf Fink, Michael Schroeter, Maria Adele Rueger

Published in: Journal of Neuroinflammation | Issue 1/2020

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Abstract

Background

Microglia are essential to maintain cell homeostasis in the healthy brain and are activated after brain injury. Upon activation, microglia polarize towards different phenotypes. The course of microglia activation is complex and depends on signals in the surrounding milieu. Recently, it has been suggested that microglia respond to ion currents, as a way of regulating their activity and function.

Methods and results

Under the hypothesis that HCN and KCNQ/Kv7 channels impact on microglia, we studied primary rat microglia in the presence or absence of specific pharmacological blockade or RNA silencing. Primary microglia expressed the subunits HCN1-4, Kv7.2, Kv7.3, and Kv7.5. The expression of HCN2, as well as Kv7.2 and Kv7.3, varied among different microglia phenotypes. The pharmacological blockade of HCN channels by ZD7288 resulted in cell depolarization with slowly rising intracellular calcium levels, leading to enhanced survival and reduced proliferation rates of resting microglia. Furthermore, ZD7288 treatment, as well as knockdown of HCN2 RNA by small interfering RNA, resulted in an attenuation of later microglia activation—both towards the anti- and pro-inflammatory phenotype. However, HCN channel inhibition enhanced the phagocytic capacity of IL4-stimulated microglia. Blockade of Kv7/KCNQ channel by XE-991 exclusively inhibited the migratory capacity of resting microglia.

Conclusion

These observations suggest that the HCN current contributes to various microglia functions and impacts on the course of microglia activation, while the Kv7/KCNQ channels affect microglia migration. Characterizing the role of HCN channels in microglial functioning may offer new therapeutic approaches for targeted modulation of neuroinflammation as a hallmark of various neurological disorders.
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Metadata
Title
The impact of hyperpolarization-activated cyclic nucleotide-gated (HCN) and voltage-gated potassium KCNQ/Kv7 channels on primary microglia function
Authors
Sabine Ulrike Vay
Lea Jessica Flitsch
Monika Rabenstein
Helena Monière
Igor Jakovcevski
Pavle Andjus
Dunja Bijelic
Stefan Blaschke
Helene Luise Walter
Gereon Rudolf Fink
Michael Schroeter
Maria Adele Rueger
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-020-01779-4

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