NDLI: Electrophysiological Differences between the Same Pore Region Mutation in SCN1A and SCN3A

Content Provider	Springer Nature Link
Author	Chen, Y. J. Shi, Y. W. Xu, H. Q. Chen, M. L. Gao, M. M. Sun, W. W. Tang, B. Zeng, Y. Liao, W. P.
Copyright Year	2014
Abstract	Mutations in the sodium channel gene, SCN1A (Na$_{V}$1.1), have been linked to a spectrum of epilepsy syndromes, and many of these mutations occur in the pore region of the channel. Electrophysiological characterization has revealed that most SCN1A mutations in the pore region result in complete loss of function. SCN3A mutations have also been identified in patients with epilepsy; however, mutations in this pore region maintain some degree of electrophysiological function. It is thus speculated that compared to SCN3A disruptions, SCN1A mutations have a more pronounced effect on electrophysiological function. In this study, we identified a novel mutation, N302S, in the SCN3A pore region of a child with epilepsy. To investigate if mutations at the pore regions of SCN3A and SCN1A have different impacts on channel function, we studied the electrophysiological properties of N302S in Na$_{V}$1.3 and its homologous mutation (with the same amino acid substitution) in Na$_{V}$1.1 (N301S). Functional analysis demonstrated that SCN1A-N301S had no measurable sodium current, indicating a complete loss of function, while SCN3A-N302S slightly reduced channel activity. This observation indicates that the same pore region mutation affects SCN1A more than SCN3A. Our study further revealed a huge difference in electrophysiological function between SCN1A and SCN3A mutations in the pore region; this might explain the more common SCN1A mutations detected in patients with epilepsy and the more severe phenotypes associated with these mutations.
Starting Page	1263
Ending Page	1270
Page Count	8
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	51
Issue Number	3
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2014-07-03
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	SCN1A SCN3A Pore region mutation Electrophysiological properties Epilepsy Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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