Dravet Variant SCN1A ^A1783V Impairs Interneuron Firing Predominantly by Altered Channel Activation.

ABSTRACT: Dravet syndrome (DS) is a developmental epileptic encephalopathy mainly caused by functional Na_V1.1 haploinsufficiency in inhibitory interneurons. Recently, a new conditional mouse model expressing the recurrent human p.(Ala1783Val) missense variant has become available. In this study, we provided an electrophysiological characterization of this variant in tsA201 cells, revealing both altered voltage-dependence of activation and slow inactivation without reduced sodium peak current density. Based on these data, simulated interneuron (IN) firing properties in a conductance-based single-compartment model suggested surprisingly similar firing deficits for Na_V1.1^A1783V and full haploinsufficiency as caused by heterozygous truncation variants. Impaired Na_V<

SUBMITTER: Layer N 

PROVIDER: S-EPMC8581729 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature