Biophysical basis for Kv1.3 regulation of membrane potential changes induced by P2X4-mediated calcium entry in microglia.

Glia
Hai M NguyenHeike Wulff

Abstract

Microglia-mediated inflammation exerts adverse effects in ischemic stroke and in neurodegenerative disorders such as Alzheimer's disease (AD). Expression of the voltage-gated potassium channel Kv1.3 is required for microglia activation. Both genetic deletion and pharmacological inhibition of Kv1.3 are effective in reducing microglia activation and the associated inflammatory responses, as well as in improving neurological outcomes in animal models of AD and ischemic stroke. Here we sought to elucidate the molecular mechanisms underlying the therapeutic effects of Kv1.3 inhibition, which remain incompletely understood. Using a combination of whole-cell voltage-clamp electrophysiology and quantitative PCR (qPCR), we first characterized a stimulus-dependent differential expression pattern for Kv1.3 and P2X4, a major ATP-gated cationic channel, both in vitro and in vivo. We then demonstrated by whole-cell current-clamp experiments that Kv1.3 channels contribute not only to setting the resting membrane potential but also play an important role in counteracting excessive membrane potential changes evoked by depolarizing current injections. Similarly, the presence of Kv1.3 channels renders microglia more resistant to depolarization pr...Continue Reading

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Citations

Sep 17, 2020·International Journal of Molecular Sciences·Eunyoung KimSang Seong Kim
Dec 29, 2020·Glia·Anthony D Umpierre, Long-Jun Wu
Jul 3, 2021·Cells·Ivó H HernándezMaría José Pérez-Álvarez
Oct 8, 2021·Annals of Clinical and Translational Neurology·Yi-Je ChenHeike Wulff

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Datasets Mentioned

BETA
X93565

Methods Mentioned

BETA
transfection
PCR
fluorescence microscopy
transgenic

Software Mentioned

Origin
HEKA PatchMaster

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