Sodium channel mutations causing generalized epilepsy with febrile seizures + (Barela et al. 2006)

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Accession:87585
A novel mutation, R859C, in the Nav1.1 sodium channel was identified in a 4-generation, 33-member Caucasian family with a clinical presentation consistent with GEFS+. The mutation neutralizes a positively charged arginine in the domain 2 S4 voltage sensor of the Nav1.1 channel Ą subunit. When the mutation was placed in the rat Nav1.1 channel and expressed in Xenopus oocytes, the mutant channel displayed a positive shift in the voltage-dependence of sodium channel activation, slower recovery from slow inactivation, and lower levels of current compared to the wild-type channel. Computational analysis suggests that neurons expressing the mutant channel have higher thresholds for firing a single action potential and for firing multiple action potentials, along with decreased repetitive firing. Therefore, this mutation should lead to decreased neuronal excitability, in contrast to most previous GEFS+ sodium channel mutations that have changes predicted to increase neuronal firing.
References:
1 . Barela AJ, Waddy SP, Lickfett JG, Hunter J, Anido A, Helmers SL, Goldin AL, Escayg A (2006) An Epilepsy Mutation in the Sodium Channel SCN1A That Decreases Channel Excitability J. Neurosci. 26(10):2714-2723 [PubMed]
2 . Spampanato J, Aradi I, Soltesz I, Goldin AL (2004) Increased neuronal firing in computer simulations of sodium channel mutations that cause generalized epilepsy with febrile seizures plus. J Neurophysiol 91:2040-50 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): I Na,t; I K; I Sodium;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.1 SCN1A;
Transmitter(s):
Simulation Environment: NEURON; NEURONPM (web link to tool);
Model Concept(s): Action Potentials; Epilepsy;
Implementer(s): Lickfett, Jay ; Goldin, Al [agoldin at uci.edu];
Search NeuronDB for information about:  I Na,t; I K; I Sodium;
 
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R859C
                            
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