Mind the translational gap: human microglia differ from mouse microglia in their regulation of Kv and Kir2.1 channels

Bibliographic Details
Title: Mind the translational gap: human microglia differ from mouse microglia in their regulation of Kv and Kir2.1 channels
Authors: Schilling, Simone, Felk, Jessica, Kikhia, Majed, Podesta, Alice, Hintze, Johanna, Fidzinski, Pawel, Holtkamp, Martin, Onken, Julia, Sauvigny, Thomas, Kalbhenn, Thilo, Simon, Matthias, Kettenmann, Helmut, Endres, Matthias, Goettert, Ria, Gertz, Karen
Publisher Information: Cold Spring Harbor Laboratory Press
Publication Year: 2026
Collection: Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository
Subject Terms: Function and Dysfunction of the Nervous System, Topic 2: Molecular Processes and Therapies
Description: K(+) channels are important for controlling membrane potential and regulating functional (K(ir)) channel 2.1 modulates proliferation, voltage-gated K(+) channels (K(v)) are linked to inflammatory response in mouse microglia (mMG). These channels serve as possible drug targets but little is known regarding their activity in human microglia. We used patch-clamp recording to study membrane currents of primary human microglia (hMG) and human induced pluripotent stem cell-derived microglia-like cells (hiPSC-MGL) and compared them with mMG. Unlike mMG, hMG and hiPSC-MGL exhibited K(ir)2.1 currents only after LPS+IFN-γ stimulation. Interestingly, K(v) currents were not observed in hMG or hiPSC-MGL under any condition. While mMG had a progressively ameboid morphology after stimulation, hMG showed few morphological changes and hiPSC-MGL increased ramification. Overall, the activity of K(ir)2.1 and K(v) channels in hMG and hiPSC-MGL differs fundamentally from mMG. Our findings highlight differences between species and underscore the need for translational approaches.
Document Type: report
File Description: application/pdf
Language: English
Relation: https://edoc.mdc-berlin.de/id/eprint/26294/1/26294oa.pdf; https://edoc.mdc-berlin.de/id/eprint/26294/2/26294suppl.pdf; Mind the translational gap: human microglia differ from mouse microglia in their regulation of Kv and Kir2.1 channels. Schilling, Simone, Felk, Jessica, Kikhia, Majed, Podesta, Alice, Hintze, Johanna, Fidzinski, Pawel, Holtkamp, Martin, Onken, Julia, Sauvigny, Thomas, Kalbhenn, Thilo, Simon, Matthias, Kettenmann, Helmut, Endres, Matthias, Goettert, Ria and Gertz, Karen bioRxiv : 2026.03.10.710589. 10 March 2026; bioRxiv:2026.03.10.710589; https://doi.org/10.64898/2026.03.10.710589
DOI: 10.64898/2026.03.10.710589
Availability: https://edoc.mdc-berlin.de/id/eprint/26294/
https://edoc.mdc-berlin.de/26294/
https://doi.org/10.64898/2026.03.10.710589
Rights: cc_by_4
Accession Number: edsbas.EEA117E4
Database: BASE
Description
DOI:10.64898/2026.03.10.710589