ArticleBrain : a journal of neurology2016
Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.
Article in Brain : a journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- Neuromuscular junction failure in sarcopenia is linked to NaV1.4 loss and reversed by ClC-1 inhibition.The Journal of clinical investigation · 2026Article
- Zebrafish fast muscle contractions avoid the mammalian requirement for voltage-gated Na+ channels.PLoS biology · 2025Article
- Molecular genetics of skeletal muscle channelopathies.Journal of human genetics · 2025Review
- Normal locomotion in zebrafish lacking the sodium channel NaV1.4 suggests that the need for muscle action potentials is not universal.PLoS biology · 2025Article
- Hydrops fetalis due to loss of function of hNav1.4 channel via compound heterozygous variants.Journal of human genetics · 2025Article
- Novel compound heterozygous mutations inHeliyon · 2024Article
- Periodic paralysis.Handbook of clinical neurology · 2024Review
- Distinguishing Loss-of-Function and Gain-of-FunctionNeurology. Genetics · 2023Article
- Case report: NovelFrontiers in pediatrics · 2022Article
- New Challenges Resulting From the Loss of Function of NaFrontiers in pharmacology · 2021Review
- Homozygous C-terminal loss-of-function NaJournal of neurology, neurosurgery, and psychiatry · 2020Article
- β2-Adrenergic receptor agonists ameliorate the adverse effect of long-term pyridostigmine on neuromuscular junction structure.Brain : a journal of neurology · 2019Article
- Article
- A204E mutation in NaScientific reports · 2018Article
- Hypokalaemic periodic paralysis and myotonia in a patient with homozygous mutation p.R1451L in NaScientific reports · 2018Article
- Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.Lancet (London, England) · 2018Article
- Substitutions of the S4DIV R2 residue (R1451) in NaScientific reports · 2018Article
- Sodium Channelopathies of Skeletal Muscle.Handbook of experimental pharmacology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Over 60 mutations of SCN4A encoding the NaV1.4 sodium channel of skeletal muscle have been identified in patients with myotonia, periodic paralysis, myasthenia, or congenital myopathy. Most mutations are missense with gain-of-function defects that cause susceptibility to myotonia or periodic paralysis. Loss-of-function from enhanced inactivation or null alleles is rare and has been associated with myasthenia and congenital myopathy, while a mix of loss and gain of function changes has an uncertain relation to hypokalaemic periodic paralysis. To better define the functional consequences for a loss-of-function, we generated NaV1.4 null mice by deletion of exon 12. Heterozygous null mice have latent myasthenia and a right shift of the force-stimulus relation, without evidence of periodic paralysis. Sodium current density was half that of wild-type muscle and no compensation by retained expression of the foetal NaV1.5 isoform was detected. Mice null for NaV1.4 did not survive beyond the second postnatal day. This mouse model shows remarkable preservation of muscle function and viability for haploinsufficiency of NaV1.4, as has been reported in humans, with a propensity for pseudo-myasthenia caused by a marginal Na(+) current density to support sustained high-frequency action potentials in muscle.
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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.