Impaired excitability of fast-spiking neurons in a novel mouse model of <i>KCNC1</i> epileptic encephalopathy.

ABSTRACT: The recurrent pathogenic variant KCNC1-p.Ala421Val (A421V) is a cause of developmental and epileptic encephalopathy characterized by moderate-to-severe developmental delay/intellectual disability, and infantile-onset treatment-resistant epilepsy with multiple seizure types including myoclonic seizures. Yet, the mechanistic basis of disease is unclear. KCNC1 encodes Kv3.1, a voltage-gated potassium channel subunit that is highly and selectively expressed in neurons capable of generating action potentials at high frequency, including parvalbumin-positive fast-spiking GABAergic inhibitory interneurons in cerebral cortex (PV-INs) known to be important for cognitive function and plasticity as well as control of network excitation to prevent seizures. In this study, we generate a n

SUBMITTER: Wengert ER 

PROVIDER: S-EPMC11463657 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature