Heterozygous expression of a <i>Kcnt1</i> gain-of-function variant has differential effects on somatostatin- and parvalbumin-expressing cortical GABAergic neurons.

ABSTRACT: More than 20 recurrent missense gain-of-function (GOF) mutations have been identified in the sodium-activated potassium (K_Na) channel gene KCNT1 in patients with severe developmental and epileptic encephalopathies (DEEs), most of which are resistant to current therapies. Defining the neuron types most vulnerable to KCNT1 GOF will advance our understanding of disease mechanisms and provide refined targets for precision therapy efforts. Here, we assessed the effects of heterozygous expression of a Kcnt1 GOF variant (Kcnt1^Y777H) on K_Na currents and neuronal physiology among cortical glutamatergic and GABAergic neurons in mice, including those expressing vasoactive intestinal polypeptide (VIP), somatostatin (SST), and parvalbumin (PV), to i

SUBMITTER: Shore AN 

PROVIDER: S-EPMC11469685 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature