Kv7.2 loss-of-function causes early hyperexcitability and network remodelling

Clicks: 1
ID: 316095
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal

Ranked #370 of 375 articles by views in Brain research

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 375 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Loss-of-function (LOF) variants in KCNQ2, encoding the potassium channel subunit Kv7.2, cause a spectrum of neonatal epilepsies ranging from self-limiting familial neonatal epilepsy (SeLFNE) to severe developmental and epileptic encephalopathy (DEE). To dissect the developmental consequences of Kv7.2 LOF, we conducted a longitudinal and multimodal comparative analysis in a human neuronal model generated from patients with KCNQ2-DEE and KCNQ2-SeLFNE. KCNQ2-LOF variants induced a biphasic dysfunction at both single-cell and network levels, characterized by early Kv7-driven hyperexcitability accompanied by a clear reduction M-current density, which was rescued by acute Retigabine treatment. At later stages, intrinsic excitability and M-current normalized, yet network activity diverged further from control trajectories, indicating compensatory and ultimately maladaptive network remodeling. Transcriptomic analysis mirrored this biphasic dynamic trajectory, revealing an initial upregulation followed by a subsequent downregulation of synaptic genes. Structural analysis showed a steeper decline in presynaptic density alongside a distal shift in the axon initial segment (AIS) throughout maturation, and impaired AIS plasticity at later stages. Overall, KCNQ2-LOF variants disrupt human neuronal maturation through dynamic, biphasic changes in function, gene expression and structure, offering insights into disease mechanisms and therapeutic options.
Reference Key
openalex_W7163737920 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Nina Dirkx, Marcus Kaji, Els De Vriendt, Giusy Carleo, Francesco Miceli, Bob Asselbergh, Peter Verstraelen, N. Zonnekein, Lidia Carotenuto, Louis T. Dang, Vera Sommers, Eve Vlaemynck, Lieven Lagae, Berten Ceulemans, Peter De Jonghe, Winnok H. De Vos, Maurizio Taglialatela, Sarah Weckhuysen
Journal Brain research
Year 2026
DOI
10.1093/brain/awag199
URL
https://doi.org/10.1093/brain/awag199
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.