BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models.

ABSTRACT: KCNMA1 forms the pore of BK K⁺ channels, which regulate neuronal and muscle excitability. Recently, genetic screening identified heterozygous KCNMA1 variants in a subset of patients with debilitating paroxysmal non-kinesigenic dyskinesia, presenting with or without epilepsy (PNKD3). However, the relevance of KCNMA1 mutations and the basis for clinical heterogeneity in PNKD3 has not been established. Here, we evaluate the relative severity of three KCNMA1 patient variants in BK channels, neurons, and mice. In heterologous cells, BK^N999S and BK^D434G channels displayed gain-of-function (GOF) properties, whereas BK^H444Q channels showed loss-of-function (LOF) properties. The relative degree of channel activity was BK^N999S

SUBMITTER: Park SM 

PROVIDER: S-EPMC9275823 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature