ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Effects in neocortical neurons of mutations of the Na(v)1.2 Na+ channel causing benign familial neonatal-infantile seizures.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 117 citations in OpenAlex.
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- Development and Adaptive Function in Individuals WithNeurology · 2025Article
- Voltage-gated sodium channels in genetic epilepsy: up and down of excitability.Journal of neurochemistry · 2024Review
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- Therapeutic efficacy of voltage-gated sodium channel inhibitors in epilepsy.Acta epileptologica · 2023Review
- Loss or gain of function? Effects of ion channel mutations on neuronal firing depend on the neuron type.Frontiers in neurology · 2023Article
- Cellular and behavioral effects of altered NaV1.2 sodium channel ion permeability in Scn2aK1422E mice.Human molecular genetics · 2022Article
- Cannabidiol and Sodium Channel Pharmacology: General Overview, Mechanism, and Clinical Implications.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Review
- Functional correlates of clinical phenotype and severity in recurrent SCN2A variants.Communications biology · 2022Article
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- All our knowledge begins with the antisenses.The Journal of clinical investigation · 2021Article
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
- Epilepsy Syndromes in the First Year of Life and Usefulness of Genetic Testing for Precision Therapy.Genes · 2021Review
- Sodium channelopathies in neurodevelopmental disorders.Nature reviews. Neuroscience · 2021Review
- Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment.International journal of molecular sciences · 2020Review
- Prickle2 and Igsf9b Coordinately Regulate the Cytoarchitecture of the Axon Initial Segment.Cell structure and function · 2020Article
- The neonatal SCN2A mutant channel mimics adult channel properties.The Journal of general physiology · 2020Article
- Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations of voltage-gated Na+ channels are the most common cause of familial epilepsy. Benign familial neonatal-infantile seizures (BFNIS) is an epileptic trait of the early infancy, and it is the only well characterized epileptic syndrome caused exclusively by mutations of Na(V)1.2 Na+ channels, but no functional studies of BFNIS mutations have been done. The comparative study of the functional effects and the elucidation of the pathogenic mechanisms of epileptogenic mutations is essential for designing targeted and effective therapies. However, the functional properties of Na+ channels and the effects of their mutations are very sensitive to the cell background and thus to the expression system used. We investigated the functional effects of four of the six BFNIS mutations identified (L1330F, L1563V, R223Q, and R1319Q) using as expression system transfected pyramidal and bipolar neocortical neurons in short primary cultures, which have small endogenous Na+ current and thus permit the selective study of transfected channels. The mutation L1330F caused a positive shift of the inactivation curve, and the mutation L1563V caused a negative shift of the activation curve, effects that are consistent with neuronal hyperexcitability. The mutations R223Q and R1319Q mainly caused positive shifts of both activation and inactivation curves, effects that cannot be directly associated with a specific modification of excitability. Using physiological stimuli in voltage-clamp experiments, we showed that these mutations increase both subthreshold and action Na+ currents, consistently with hyperexcitability. Thus, the pathogenic mechanism of BFNIS mutations is neuronal hyperexcitability caused by increased Na+ current.
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