Anti-seizure mechanisms of midazolam and valproate at the β2(L51M) variant of the GABA_A receptor.

ABSTRACT: Genetic sequencing is identifying an expanding number of variants of GABA_A receptors associated with human epilepsies. We identified a new de novo variant of the β2 subunit (β2L51M) of the inhibitory GABA_A receptor associated with seizures. Our analysis determined the pathogenicity of the variant and the effects of anti-seizure medications. Our data demonstrates that the variant reduced cell surface trafficking and peak GABA-gated currents. Synaptic currents mediated by variant-containing receptors decayed faster than wild-type and single receptor currents showed that the variant shortened the duration of receptor activity by decreasing receptor open times. We tested the effects of the anti-seizure medications, midazolam, carbamazepine and valproate and found that all

SUBMITTER: Kuanyshbek A 

PROVIDER: S-EPMC9981329 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature