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Data
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Sodium channel mutations causing generalized epilepsy with febrile seizures + (Barela et al. 2006)
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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.
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Neuron or other electrically excitable cell Show
Other
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Barela AJ, Waddy SP, Lickfett JG, Hunter J, Anido A, Helmers SL, Goldin AL, Escayg A (2006) Show
Other
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Spampanato J, Aradi I, Soltesz I, Goldin AL (2004) Show
Other
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87585
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agoldin@uci.edu
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