ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Regulation of persistent Na current by interactions between beta subunits of voltage-gated Na channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.Pflugers Archiv : European journal of physiology · 2024Pooled it
- Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons.Molecular pain · 2012Trial
- A Novel Mouse Model for Developmental and Epileptic Encephalopathy by Purkinje Cell-Specific Deletion ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
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- Ataxia and cerebellar hypoexcitability in a mouse model of SCN1B-linked Dravet syndrome.JCI insight · 2025Article
- Effects of open-channel blocking peptides in NaBiophysical journal · 2025Article
- Article
- Structural basis for the rescue of hyperexcitable cells by the amyotrophic lateral sclerosis drug Riluzole.Nature communications · 2024Article
- Resurgent current in context: Insights from the structure and function of Na and K channels.Biophysical journal · 2024Review
- The Hodgkin-Huxley-Katz Prize Lecture: A Markov model with permeation-dependent gating that accounts for resurgent current of voltage-gated Na channels.The Journal of physiology · 2023Article
- A Push-Pull Mechanism Between PRRT2 and β4-subunit Differentially Regulates Membrane Exposure and Biophysical Properties of NaV1.2 Sodium Channels.Molecular neurobiology · 2023Article
- Cryo-EM structure of human voltage-gated sodium channel NaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Modulation of neuronal excitability by binge alcohol drinking.Frontiers in molecular neuroscience · 2023Review
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy.Children (Basel, Switzerland) · 2022Review
- Chemical and Biological Tools for the Study of Voltage-Gated Sodium Channels in Electrogenesis and Nociception.Chembiochem : a European journal of chemical biology · 2022Review
- Article
- Ranolazine: An Old Drug with Emerging Potential; Lessons from Pre-Clinical and Clinical Investigations for Possible Repositioning.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells.Cells · 2021Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The beta subunits of voltage-gated Na channels (Scnxb) regulate the gating of pore-forming alpha subunits, as well as their trafficking and localization. In heterologous expression systems, beta1, beta2, and beta3 subunits influence inactivation and persistent current in different ways. To test how the beta4 protein regulates Na channel gating, we transfected beta4 into HEK (human embryonic kidney) cells stably expressing Na(V)1.1. Unlike a free peptide with a sequence from the beta4 cytoplasmic domain, the full-length beta4 protein did not block open channels. Instead, beta4 expression favored open states by shifting activation curves negative, decreasing the slope of the inactivation curve, and increasing the percentage of noninactivating current. Consequently, persistent current tripled in amplitude. Expression of beta1 or chimeric subunits including the beta1 extracellular domain, however, favored inactivation. Coexpressing Na(V)1.1 and beta4 with beta1 produced tiny persistent currents, indicating that beta1 overcomes the effects of beta4 in heterotrimeric channels. In contrast, beta1(C121W), which contains an extracellular epilepsy-associated mutation, did not counteract the destabilization of inactivation by beta4 and also required unusually large depolarizations for channel opening. In cultured hippocampal neurons transfected with beta4, persistent current was slightly but significantly increased. Moreover, in beta4-expressing neurons from Scn1b and Scn1b/Scn2b null mice, entry into inactivated states was slowed. These data suggest that beta1 and beta4 have antagonistic roles, the former favoring inactivation, and the latter favoring activation. Because increased Na channel availability may facilitate action potential firing, these results suggest a mechanism for seizure susceptibility of both mice and humans with disrupted beta1 subunits.
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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.