ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Sodium channel blockers for neuroprotection in multiple sclerosis.The Cochrane database of systematic reviews · 2015Pooled it
- Calmodulin acts as a selective switch in FGF12A-mediated regulation of the cardiac sodium channel Nav1.5.The Journal of biological chemistry · 2026Article
- Calcium interaction with Nav1.5 via FGF12A and CaM binding.bioRxiv : the preprint server for biology · 2026Article
- Optic nerve injury impairs intrinsic mechanisms underlying electrical activity in a resilient retinal ganglion cell.The Journal of physiology · 2025Article
- α4β2The Journal of physiology · 2025Article
- Direct binding of calmodulin to the cytosolic C-terminal regions of sweet/umami taste receptors.Journal of biochemistry · 2023Article
- NaV1.6 dysregulation within myocardial T-tubules by D96V calmodulin enhances proarrhythmic sodium and calcium mishandling.The Journal of clinical investigation · 2023Article
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- Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases.International journal of molecular sciences · 2022Review
- Calmodulin Interactions with Voltage-Gated Sodium Channels.International journal of molecular sciences · 2021Review
- Review
- Structure and function of the calcium-selective TRP channel TRPV6.The Journal of physiology · 2021Review
- The difficulty to model Huntington's disease in vitro using striatal medium spiny neurons differentiated from human induced pluripotent stem cells.Scientific reports · 2021Article
- CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability.The Journal of biological chemistry · 2020Article
- Nodes of Ranvier during development and repair in the CNS.Nature reviews. Neurology · 2020Review
- Article
- Distinct functional alterations in SCN8A epilepsy mutant channels.The Journal of physiology · 2020Article
- mGluR5-dependent modulation of dendritic excitability in CA1 pyramidal neurons mediated by enhancement of persistent NaThe Journal of physiology · 2018Article
- Mechanism of calmodulin inactivation of the calcium-selective TRP channel TRPV6.Science advances · 2018Article
- Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway.Cell reports · 2018Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Modulation of voltage-gated sodium channels (VGSC) can have a major impact on cell excitability. Analysis of calmodulin (CaM) binding to GST-fusion proteins containing the C-terminal domains of Nav1.1-Nav1.9 indicates that some of the tetrodotoxin-sensitive VGSC isoforms, including NaV1.4 and NaV1.6, are able to bind CaM in a calcium-independent manner. Here we demonstrate that association with CaM is important for functional expression of NaV1.4 and NaV1.6 VGSCs. Disrupting the interaction between CaM and the C terminus of NaV1.4 and NaV1.6 channels reduced current amplitude by 99 and 62%, respectively. Overexpression of CaM increased the current generated by Nav1.4 and Nav1.6 C-terminal mutant constructs that exhibited intermediate current densities and intermediate binding affinities for CaM, demonstrating that this effect on current density was directly dependent on the ability of the C terminus to bind CaM. In addition to the effects on current density, calmodulin also was able to modulate the inactivation kinetics of Nav1.6, but not Nav1.4, currents in a calcium-dependent manner. Our data demonstrate that CaM can regulate the properties of VGSCs via calcium-dependent and calcium-independent mechanisms and suggest that modulation of neuronal sodium channels may play a role in calcium-dependent neuronal plasticity.
Indexed as
Identifiers
12967988PMC6740705W2147001406What 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.