ArticleBiochimica et biophysica acta2015
The Nav1.2 channel is regulated by GSK3.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- mTORC2-NaChannels (Austin, Tex.) · 2026Article
- Nanoscale organization in the cell membrane dynamically modulates the biophysics of voltage-gated sodium channels.Nature communications · 2026Article
- Genome-wide identification and expression analysis of the SHAGGY-like kinase gene family in foxtail millet (Frontiers in plant science · 2026Article
- A distinct PP2A subunit regulates local protein phosphorylation at the axon initial segment.Nature communications · 2025Article
- Inhibition of the GSK3β/Nav1.6 complex suppresses early-stage Alzheimer's hyperexcitability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Crosstalk among WEE1 Kinase, AKT, and GSK3 in Nav1.2 Channelosome Regulation.International journal of molecular sciences · 2024Article
- Targeted suppression of mTORC2 reduces seizures across models of epilepsy.Nature communications · 2023Article
- Determinants of iFGF13-mediated regulation of myocardial voltage-gated sodium (NaV) channels in mouse.The Journal of general physiology · 2023Article
- Therapeutic efficacy of voltage-gated sodium channel inhibitors in epilepsy.Acta epileptologica · 2023Review
- GSK-3β Disrupts Neuronal Oscillatory Function to Inhibit Learning and Memory in Male Rats.Cellular and molecular neurobiology · 2022Article
- Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases.International journal of molecular sciences · 2022Review
- Glycogen synthase kinase 3 beta inhibitor SB216763 improves Kir2.1 expression after myocardia infraction in rats.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2022Article
- Inhibition of the Akt/PKB Kinase Increases NaInternational journal of molecular sciences · 2022Article
- Pharmacologically Targeting the Fibroblast Growth Factor 14 Interaction Site on the Voltage-Gated NaInternational journal of molecular sciences · 2021Article
- Article
- Properties of Calmodulin Binding to NaNeurochemical research · 2021Article
- Inhibition of AKT Signaling Alters βIV Spectrin Distribution at the AIS and Increases Neuronal Excitability.Frontiers in molecular neuroscience · 2021Article
- The Ketamine Antidepressant Story: New Insights.Molecules (Basel, Switzerland) · 2020Review
- JAK2 regulates Nav1.6 channel function via FGF14Biochimica et biophysica acta. Molecular cell research · 2020Article
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPhosphorylation plays an essential role in regulating voltage-gated sodium (Na(v)) channels and excitability. Yet, a surprisingly limited number of kinases have been identified as regulators of Na(v) channels. We posited that glycogen synthase kinase 3 (GSK3), a critical kinase found associated with numerous brain disorders, might directly regulate neuronal Na(v) channels.
methodsWe used patch-clamp electrophysiology to record sodium currents from Na(v)1.2 channels stably expressed in HEK-293 cells. mRNA and protein levels were quantified with RT-PCR, Western blot, or confocal microscopy, and in vitro phosphorylation and mass spectrometry to identify phosphorylated residues.
resultsWe found that exposure of cells to GSK3 inhibitor XIII significantly potentiates the peak current density of Na(v)1.2, a phenotype reproduced by silencing GSK3 with siRNA. Contrarily, overexpression of GSK3β suppressed Na(v)1.2-encoded currents. Neither mRNA nor total protein expression was changed upon GSK3 inhibition. Cell surface labeling of CD4-chimeric constructs expressing intracellular domains of the Na(v)1.2 channel indicates that cell surface expression of CD4-Na(v)1.2 C-tail was up-regulated upon pharmacological inhibition of GSK3, resulting in an increase of surface puncta at the plasma membrane. Finally, using in vitro phosphorylation in combination with high resolution mass spectrometry, we further demonstrate that GSK3β phosphorylates T(1966) at the C-terminal tail of Na(v)1.2.
conclusionThese findings provide evidence for a new mechanism by which GSK3 modulates Na(v) channel function via its C-terminal tail. GENERAL SIGNIFICANCE: These findings provide fundamental knowledge in understanding signaling dysfunction common in several neuropsychiatric disorders.
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