Functional analysis of three Na_v1.6 mutations causing early infantile epileptic encephalopathy.

ABSTRACT: The voltage-gated sodium channel Na_v1.6 is associated with more than 300 cases of epileptic encephalopathy. Na_v1.6 epilepsy-causing mutations are spread over the entire channel's structure and only 10% of mutations have been characterized at the molecular level, with most of them being gain of function mutations. In this study, we analyzed three previously uncharacterized Na_v1.6 epilepsy-causing mutations: G214D, N215D and V216D, located within a mutation hot-spot at the S3-S4 extracellular loop of Domain1. Voltage clamp experiments showed a 6-16 mV hyperpolarizing shift in the activation mid-point for all three mutants. V216D presented the largest shift along with decreased current amplitude, enhanced inactivation and a lack of persistent current. Recordin

SUBMITTER: Sole L 

PROVIDER: S-EPMC7680399 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature