Disease-associated KCNMA1 variants decrease circadian clock robustness in channelopathy mouse models.

ABSTRACT: KCNMA1 encodes the voltage- and calcium-activated K+ (BK) channel, which regulates suprachiasmatic nucleus (SCN) neuronal firing and circadian behavioral rhythms. Gain-of-function (GOF) and loss-of-function (LOF) alterations in BK channel activity disrupt circadian behavior, but the effect of human disease-associated KCNMA1 channelopathy variants has not been studied on clock function. Here, we assess circadian behavior in two GOF and one LOF mouse lines. Heterozygous Kcnma1N999S/WT and homozygous Kcnma1D434G/D434G mice are validated as GOF models of paroxysmal dyskinesia (PNKD3), but whether circadian rhythm is affected in this hypokinetic locomotor disorder is unknown. Conversely, homozygous LOF Kcnma1H444Q/H444Q mice do not demonstrate PNKD3. We assessed circadian behavior by locomotor

SUBMITTER: Dinsdale RL 

PROVIDER: S-EPMC10510740 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature