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Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures
- Source :
- Scientific Reports.
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
Abstract
- Dravet syndrome is the prototype of SCN1A-mutation associated epilepsies. It is characterised by prolonged seizures, typically provoked by fever. We describe the evaluation of an SCN1A mutation in a child with early-onset temperature-sensitive seizures.The patient carries a heterozygous miss-sense variant (c3818C>T; pAla1273Val) in the NaV1.1 brain sodium channel. We characterised the functional effects of the variant using patch clamp recordings on Chinese Hamster Ovary Cells at different temperatures (32, 37, and 40°C).The variant channels produced a temperature-dependent destabilization of channel activation and fast inactivation. Implementing these empirical abnormalities in a computational model produces a higher threshold for depolarization block in the variant, particularly at 40°C, suggesting a failure to autoregulate at high-input states.These results reveal direct effects of abnormalities in biophysical NaV1.1 channel properties on neuronal dynamics. They illustrate the value of combining cellular measurements with computational models to integrate different scales (gene/channel to patient) of observations.
- Subjects :
- 0303 health sciences
Chemistry
Chinese hamster ovary cell
Sodium channel
Dynamics (mechanics)
Depolarization
Scn1a mutation
medicine.disease
03 medical and health sciences
0302 clinical medicine
Dravet syndrome
Degree Celsius
medicine
Patch clamp
Neuroscience
030217 neurology & neurosurgery
030304 developmental biology
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....c60282eaf573986e59d5819eed5e4faa
- Full Text :
- https://doi.org/10.1038/srep31879