ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Impaired inactivation gate stabilization predicts increased persistent current for an epilepsy-associated SCN1A mutation.
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 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- 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
- An in silico and in vitro human neuronal network model reveals cellular mechanisms beyond NaStem cell reports · 2023Article
- DecipheringFrontiers in cellular neuroscience · 2021Article
- Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies.Pharmacological reviews · 2018Review
- Nonlinear effects of hyperpolarizing shifts in activation of mutant NaJournal of neurophysiology · 2017Article
- Is realistic neuronal modeling realistic?Journal of neurophysiology · 2016Review
- Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures.Scientific reports · 2016Article
- Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol.Brain : a journal of neurology · 2016Article
- Genetic studies of Polish migraine patients: screening for causative mutations in four migraine-associated genes.Human genomics · 2016Article
- A gating model for wildtype and R1448H Nav1.4 channels in paramyotonia.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2014Article
- Activity-dependent alternative splicing increases persistent sodium current and promotes seizure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Voltage-gated sodium channel-associated proteins and alternative mechanisms of inactivation and block.Cellular and molecular life sciences : CMLS · 2012Review
- Pathophysiological role of omega pore current in channelopathies.Frontiers in pharmacology · 2012Article
- Nav 1.1 dysfunction in genetic epilepsy with febrile seizures-plus or Dravet syndrome.The European journal of neuroscience · 2011Article
- Ranolazine selectively blocks persistent current evoked by epilepsy-associated Naν1.1 mutations.British journal of pharmacology · 2010Article
- NaV1.1 channels and epilepsy.The Journal of physiology · 2010Review
- Coupling and cooperativity in voltage activation of a limited-state BK channel gating in saturating Ca2+.The Journal of general physiology · 2010Article
- Regulation of persistent Na current by interactions between beta subunits of voltage-gated Na channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Ionic mechanisms of endogenous bursting in CA3 hippocampal pyramidal neurons: a model study.PloS one · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Mutations in SCN1A (encoding the neuronal voltage-gated sodium channel alpha1 subunit, Na(V)1.1, or SCN1A) are associated with genetic epilepsy syndromes including generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy. Here, we present the formulation and use of a computational model for SCN1A to elucidate molecular mechanisms underlying the increased persistent sodium current exhibited by the GEFS+ mutant R1648H. Our model accurately reproduces all experimentally measured SCN1A whole-cell biophysical properties including biphasic whole-cell current decay, channel activation, and entry into and recovery from fast and slow inactivation. The model predicts that SCN1A open-state inactivation results from a two-step process that can be conceptualized as initial gate closure, followed by recruitment of a mechanism ("latch") to stabilize the inactivated state. Selective impairment of the second latching step results in an increase in whole-cell persistent current similar to that observed for the GEFS+ mutant R1648H. These results provide a deeper level of understanding of mutant SCN1A dysfunction in an inherited epilepsy syndrome, which will enable more precise computational studies of abnormal neuronal activity in epilepsy and may help guide new targeted therapeutic strategies.
Indexed as
Identifiers
What 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.