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@ARTICLE{Kapell:241120,
author = {H. Kapell and L. Fazio and J. Dyckow and S. Schwarz and A.
Cruz-Herranz and C. Mayer and J. Campos and E. D Este and W.
Möbius and C. Cordano and A.-K. Pröbstel and M.
Gharagozloo and A. Zulji and V. Narayanan Naik and A.-K.
Delank and M. Cerina and T. Müntefering and C. Lerma-Martin
and J. K. Sonner and J. H. Sin and P. Disse and N. Rychlik
and K. Sabeur and M. Chavali and R. Srivastava and M.
Heidenreich and K. C. Fitzgerald and G. Seebohm and C.
Stadelmann and B. Hemmer and M. Platten$^*$ and T. J.
Jentsch and M. Engelhardt and T. Budde and K.-A. Nave and P.
A. Calabresi and M. A. Friese and A. J. Green and C. Acuna
and D. H. Rowitch and S. G. Meuth and L. Schirmer},
title = {{N}euron-oligodendrocyte potassium shuttling at nodes of
{R}anvier protects against inflammatory demyelination.},
journal = {The journal of clinical investigation},
volume = {133},
number = {7},
issn = {0021-9738},
address = {Ann Arbor, Mich.},
publisher = {ASCJ},
reportid = {DKFZ-2023-00240},
pages = {e164223},
year = {2023},
note = {2023 Apr 3;133(7):e164223},
abstract = {Multiple sclerosis (MS) is a progressive
inflammatory-demyelinating disease of the central nervous
system. Increasing evidence suggests that vulnerable neurons
in MS exhibit fatal metabolic exhaustion over time, a
phenomenon hypothesized to be caused by chronic
hyperexcitability. Axonal Kv7 (outward rectifying) and
oligodendroglial Kir4.1 (inward rectifying) potassium
channels have important roles in regulating neuronal
excitability at and around nodes of Ranvier. Here, we
studied the spatial and functional relationship between
neuronal Kv7 and oligodendroglial Kir4.1 channels and
assessed the transcriptional and functional signatures of
cortical and retinal projection neurons under physiological
and inflammatory-demyelinating conditions. We found that
both channels became dysregulated in MS and experimental
autoimmune encephalomyelitis (EAE) with Kir4.1 channels
being chronically downregulated and Kv7 channel subunits
being transiently upregulated during inflammatory
demyelination. Further, we observed that pharmacological Kv7
channel opening with retigabine reduced neuronal
hyperexcitability in human and EAE neurons, improved
clinical EAE signs and rescued neuronal pathology in
oligodendrocyte-Kir4.1-deficient mice. In summary, our
findings indicate that neuron-oligodendrocyte compensatory
interactions promote resilience through Kv7 and Kir4.1
channels and suggest pharmacological activation of nodal Kv7
channels as a neuroprotective strategy against inflammatory
demyelination.},
keywords = {Inflammation (Other) / Multiple sclerosis (Other) /
Neurodegeneration (Other) / Neuroscience (Other) / Potassium
channels (Other)},
cin = {D170 / HD01},
ddc = {610},
cid = {I:(DE-He78)D170-20160331 / I:(DE-He78)HD01-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36719741},
doi = {10.1172/JCI164223},
url = {https://inrepo02.dkfz.de/record/241120},
}