Spontaneous seizure and memory loss in mice expressing an epileptic encephalopathy variant in the calmodulin-binding domain of K_v7.2.

ABSTRACT: Epileptic encephalopathy (EE) is characterized by seizures that respond poorly to antiseizure drugs, psychomotor delay, and cognitive and behavioral impairments. One of the frequently mutated genes in EE is KCNQ2, which encodes the K_v7.2 subunit of voltage-gated K_v7 potassium channels. K_v7 channels composed of K_v7.2 and K_v7.3 are enriched at the axonal surface, where they potently suppress neuronal excitability. Previously, we reported that the de novo dominant EE mutation M546V in human K_v7.2 blocks calmodulin binding to K_v7.2 and axonal surface expression of K_v7 channels via their intracellular retention. However, whether these pathogenic mechanisms underlie epileptic seizures and behavioral co

SUBMITTER: Kim EC 

PROVIDER: S-EPMC8713762 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature