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

KCNMA1 forms the pore of BK K channels, which regulate neuronal and muscle excitability. Recently, genetic screening identified heterozygous variants in a subset of patients with debilitating paroxysmal non-kinesigenic dyskinesia, presenting with or without epilepsy (PNKD3). However, the relevance of mutations and the basis for clinical heterogeneity in PNKD3 has not been established.

Comparative gain-of-function effects of the -N999S mutation on human BK channel properties.

, encoding the voltage- and calcium-activated potassium channel, has a pivotal role in brain physiology. Mutations in are associated with epilepsy and/or dyskinesia (PNKD3). Two mutations correlated with these phenotypes, D434G and N999S, were previously identified as producing gain-of-function (GOF) effects on BK channel activity.