Abnormal cytoskeletal remodeling but normal neuronal excitability in a mouse model of the recurrent developmental and epileptic encephalopathy-susceptibility KCNB1-p.R312H variant.

ABSTRACT: Integrin_K⁺ Channel_Complexes (IKCs), are implicated in neurodevelopment and cause developmental and epileptic encephalopathy (DEE) through mechanisms that were poorly understood. Here, we investigate the function of neocortical IKCs formed by voltage-gated potassium (Kv) channels Kcnb1 and α5β5 integrin dimers in wild-type (WT) and homozygous knock-in (KI) Kcnb1^R312H(+/+) mouse model of DEE. Kcnb1^R312H(+/+) mice suffer from severe cognitive deficit and compulsive behavior. Their brains show neuronal damage in multiple areas and disrupted corticocortical and corticothalamic connectivity along with aberrant glutamatergic vesicular transport. Surprisingly, the electrical properties of Kcnb1^R312H(+/+) pyramidal neurons are similar to those of WT neu

SUBMITTER: Bortolami A 

PROVIDER: S-EPMC11685548 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature