Evidence map›Paper›PMID 41239869›Full record

ArticleBrain : a journal of neurology2026

SUR1-TRPM4 is expressed in human epilepsy and promotes neuron hyperactivity and seizures in rodents.

Mitchell B Moyer, Svetlana Ivanova, Kaspar Keledjian, Matthew Kreinbrink, Jenna Langbein, Penghua Yang, Darrian McAfee, Ujwal Boddeti, Ziam Khan, Jemima Olu-Owotade and 8 more

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Article in Brain : a journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

18 authors.

Mitchell B MoyerDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0002-7504-1435
Svetlana IvanovaDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Kaspar KeledjianDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Matthew KreinbrinkDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Jenna LangbeinDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Penghua YangDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Darrian McAfeeDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0002-0643-0699
Ujwal BoddetiDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ziam KhanDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Jemima Olu-OwotadeDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Timothy ZhangDepartment of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
David R BenavidesDepartment of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0002-5630-8050
Joshua DiamondSurgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Kareem ZaghloulSurgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0001-8575-3578
Muznabanu BachaniDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Volodymyr GerzanichDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
J Marc SimardDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Alexander KsendzovskyDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Funding

NIH HHS
6 · The paper itself

Abstract

One-third of epilepsy patients do not achieve sufficient seizure freedom with current standard anti-seizure medications. Better understanding of the pathological mechanisms contributing to epileptogenesis is thus necessary to improve current therapies. SUR1-TRPM4 is a depolarizing ion channel minimally expressed in a healthy brain that is upregulated de novo in neurons and glia after epileptogenic CNS injuries such as traumatic brain injury and stroke. However, its role in epilepsy is not well understood. Here, we demonstrate using immunofluorescent microscopy that SUR1-TRPM4 expression is elevated in neurons within an electrographically sorted human epileptic brain compared with a non-epileptic brain obtained after resection from six drug-resistant temporal lobe epilepsy patients. Additionally, we utilized immunofluorescence and co-immunoprecipitation to observe that SUR1-TRPM4 is upregulated within the hippocampus and temporal cortex in mice after pentylenetetrazol (PTZ) kindling, a chronic model of rodent epilepsy. Pharmacologic inhibition of SUR1-TRPM4 using either the US Food and Drug Administration (FDA)-approved drug glyburide or 9-phenanthrol, as well as either constitutive or neuron-specific knockout of this channel, attenuated chronic seizure development in this model. Exogenous overexpression of SUR1-TRPM4 by plasmid transfection in neurons in vitro increased neuronal hyperexcitability in response to low Mg2+ stimulation, while pharmacologic inhibition of endogenous TRPM4 attenuated neuronal population hyperexcitation. Collectively, our results reveal that elevated SUR1-TRPM4 expression found in human and rodent epileptic neurons promotes chronic seizures by increasing neuronal excitation. These findings directly support clinical investigation of SUR1-TRPM4 inhibitors as potential anti-seizure therapies in epilepsy patients and suggest further investigations into the contribution of SUR1-TRPM4 to seizures induced by specific epileptogenic insults, such as traumatic brain injury (TBI), are warranted.

Indexed as

EpilepsyNeuronsSeizuresTRPM Cation ChannelsAdultAnimalsFemaleHumansMaleMiceMice, Inbred C57BLMiddle AgedPentylenetetrazoleRatsPentylenetetrazoleTRPM4 protein, humanTRPM4 protein, mouseTRPM Cation Channelschannelopathyepilepsyhyperexcitationion channelsseizure thresholdSUR1-TRPM4

Identifiers

PMID41239869
PMCPMC13232044

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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.