Evidence map›Paper›PMID 41456614›Full record

ArticleNeurobiology of disease2026

4-Aminopyridine induced hyperpolarizing oscillations in pediatric human epileptic tissue are network-driven potassium currents that are abolished by activation of KCNQ2-5 (Kv7.2-Kv7.5) channels.

J Keenan Kushner, Paige B Hoffman, Christine R Brzezinski, Brent R O'Neill, Todd C Hankinson, Charles C Wilkinson, Michael H Handler, Charles A Hoeffer, Allyson L Alexander

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

J Keenan KushnerDepartment of Neurosurgery, School of Medicine, University of Colorado | Anschutz Medical Campus, Aurora, CO 80045, USA; Neuroscience Graduate Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA; Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA. Electronic address: Keenan.Kushner@cuanschutz.edu.
Paige B HoffmanDepartment of Neurosurgery, School of Medicine, University of Colorado | Anschutz Medical Campus, Aurora, CO 80045, USA; Neuroscience Graduate Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Christine R BrzezinskiDepartment of Neurosurgery, School of Medicine, University of Colorado | Anschutz Medical Campus, Aurora, CO 80045, USA.
Brent R O'NeillDepartment of Neurosurgery, School of Medicine, University of Colorado | Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, CO 80045, USA.
Todd C HankinsonDepartment of Neurosurgery, School of Medicine, University of Colorado | Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, CO 80045, USA.
Charles C WilkinsonDepartment of Neurosurgery, School of Medicine, University of Colorado | Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, CO 80045, USA.
Michael H HandlerDepartment of Neurosurgery, School of Medicine, University of Colorado | Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, CO 80045, USA.
Charles A HoefferInstitute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA; Linda Crnic Institute, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Allyson L AlexanderDepartment of Neurosurgery, School of Medicine, University of Colorado | Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, CO 80045, USA. Electronic address: Allyson.Alexander@childrenscolorado.org.

Funding

Research Training-Genetics of Substance AbuseT32DA017637 · NIDA · UNIVERSITY OF COLORADO AT BOULDER · PI STITZEL, JERRY A · 2004 to 2023
$5.3M
Sleep abnormalities in Down Syndrome-related Alzheimer's diseaseR01AG083268 · NIA · UNIVERSITY OF COLORADO · PI CHARLES A HOEFFER · 2023 to 2026
$2.5M
Akt regulation of synaptic plasticity and behaviorR01NS086933 · NINDS · UNIVERSITY OF COLORADO · PI HOEFFER, CHARLES A · 2015 to 2019
$1.8M
Transdisciplinary Training in Sleep and Circadian RhythmsT32HL149646 · NHLBI · UNIVERSITY OF COLORADO · PI Kenneth P Wright · 2020 to 2026
$1.6M
Getting Excited about Cortical Malformations: Discovering the Mechanisms Leading to Seizure-prone Neurons in Malformations of Cortical DevelopmentK08NS131572 · NINDS · UNIVERSITY OF COLORADO DENVER · PI Allyson Laura Alexander · 2024 to 2026
$614k
NHLBI NIH HHS T32 HL149646NIA NIH HHS R01 AG083268NIDA NIH HHS T32 DA017637NINDS NIH HHS K08 NS131572NINDS NIH HHS R01 NS086933
6 · The paper itself

Abstract

Epilepsy is one of the most common neurological disorders worldwide. Despite the availability of many anti-seizure medicines (ASMs), about 30 % of patients with epilepsy develop drug-resistant epilepsy. Unfortunately, the mechanisms of ictogenesis in patients with drug-resistant epilepsy remain to be elucidated. Here, we used 4-aminopyridine (4-AP) to study interictal-like oscillations in human epileptic neocortex. 4-AP is a voltage-gated potassium channel blocker commonly used to induce seizure-like activity in ex vivo brain slices. We observed that 4-AP induced neuronal bursting and robust slow, hyperpolarizing oscillations (HypOs) in layer 2/3 (L2/3) pyramidal neurons (PNs). Using paired recordings, we demonstrate that neuronal bursting and HypOs are synchronized between neighboring L2/3 PNs. We also determined that 4-AP-induced HypOs are potassium currents that were not mediated by GABA

Indexed as

4-AminopyridineEpilepsyKCNQ2 Potassium ChannelNeocortexNerve NetPotassium Channel BlockersAction PotentialsChildFemaleHumansMalePyramidal Cells4-AminopyridineKCNQ2 Potassium ChannelPotassium Channel BlockersDrug-resistant epilepsyGABAHuman brain tissueM-currentNetwork oscillationsPediatric epilepsy

Identifiers

PMID41456614
PMCPMC12906913

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.