Universität zu Köln

Vay, Sabine Ulrike, Flitsch, Lea Jessica, Rabenstein, Monika, Moniere, Helena, Jakovcevski, Igor, Andjus, Pavle, Bijelic, Dunja, Blaschke, Stefan, Walter, Helene Luise, Fink, Gereon Rudolf, Schroeter, Michael and Rueger, Maria Adele (2020). The impact of hyperpolarization-activated cyclic nucleotide-gated (HCN) and voltage-gated potassium KCNQ/Kv7 channels on primary microglia function. J. Neuroinflamm., 17 (1). LONDON: BMC. ISSN 1742-2094

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vay, Sabine Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Flitsch, Lea Jessica UNSPECIFIED UNSPECIFIED UNSPECIFIED Rabenstein, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Moniere, Helena UNSPECIFIED UNSPECIFIED UNSPECIFIED Jakovcevski, Igor UNSPECIFIED UNSPECIFIED UNSPECIFIED Andjus, Pavle UNSPECIFIED UNSPECIFIED UNSPECIFIED Bijelic, Dunja UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaschke, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Helene Luise UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gereon Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueger, Maria Adele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-337533
DOI:	10.1186/s12974-020-01779-4
Journal or Publication Title:	J. Neuroinflamm.
Volume:	17
Number:	1
Date:	2020
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1742-2094
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEURAL STEM-CELLS; DISTAL DENDRITES; CATION CHANNELS; CHRONIC PHASE; K+ CHANNELS; I-H; EXPRESSION; KV1.3; NEUROINFLAMMATION; EXCITABILITY Multiple languages Immunology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33753