ArticlePloS one2017
Downregulation of KCNMB4 expression and changes in BK channel subtype in hippocampal granule neurons following seizure activity.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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.
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.
Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Overexpression of BDNF Suppresses the Epileptiform Activity in Cortical Neurons of Heterozygous Mice with a Transcription Factor Sip1 Deletion.International journal of molecular sciences · 2024Article
- Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns.BMC genomics · 2024Article
- Ethanol's interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice.Molecular psychiatry · 2024Article
- Clocking Epilepsies: A Chronomodulated Strategy-Based Therapy for Rhythmic Seizures.International journal of molecular sciences · 2023Review
- CaInternational journal of molecular sciences · 2023Review
- Multi-modal characterization and simulation of human epileptic circuitry.Cell reports · 2022Article
- Article
- Chronic ethanol exposure differentially alters neuronal function in the medial prefrontal cortex and dentate gyrus.Neuropharmacology · 2021Article
- Control of Neuronal Excitability by Cell Surface Receptor Density and Phosphoinositide Metabolism.Frontiers in pharmacology · 2021Article
- Prevention of brain damage after traumatic brain injury by pharmacological enhancement of KCNQ (Kv7, "M-type") KJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Functional responses of the hippocampus to hyperexcitability depend on directed, neuron-specific KCNQ2 KHippocampus · 2020Article
- Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis.Frontiers in neurology · 2020Review
- Review
- The absence of NIPA2 enhances neural excitability through BK (big potassium) channels.CNS neuroscience & therapeutics · 2019Article
- The Cannabinoid-Like Compound, VSN16R, Acts on Large Conductance, CaPharmaceuticals (Basel, Switzerland) · 2019Article
- Physiological Roles and Therapeutic Potential of CaFrontiers in molecular neuroscience · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
A major challenge is to understand maladaptive changes in ion channels that sets neurons on a course towards epilepsy development. Voltage- and calcium-activated K+ (BK) channels contribute to early spike timing in neurons, and studies indicate that the BK channel plays a pathological role in increasing excitability early after a seizure. Here, we have investigated changes in BK channels and their accessory β4 subunit (KCNMB4) in dentate gyrus (DG) granule neurons of the hippocampus, key neurons that regulate excitability of the hippocampus circuit. Two days after pilocarpine-induced seizures, we found that the predominant effect is a downregulation of the β4 accessory subunit mRNA. Consistent with reduced expression, single channel recording and pharmacology indicate a switch in the subtype of channels expressed; from iberiotoxin-resistant, type II BK channels (BK α/β4) that have higher channel open probability and slow gating, to iberiotoxin-sensitive type I channels (BK α alone) with low open probability and faster gating. The switch to a majority of type I channel expression following seizure activity is correlated with a loss of BK channel function on spike threshold while maintaining the channel's contribution to increased early spike frequency. Using heterozygous β4 knockout mice, we find reduced expression is sufficient to increase seizure sensitivity. We conclude that seizure-induced downregulation of KCNMB4 is an activity dependent mechanism that increases the excitability of DG neurons. These novel findings indicate that BK channel subtypes are not only defined by cell-specific expression, but can also be plastic depending on the recent history of neuronal excitability.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.