Skeletal muscle delimited myopathy and verapamil toxicity in SUR2 mutant mouse models of AIMS.

ABSTRACT: ABCC9-related intellectual disability and myopathy syndrome (AIMS) arises from loss-of-function (LoF) mutations in the ABCC9 gene, which encodes the SUR2 subunit of ATP-sensitive potassium (K_ATP ) channels. K_ATP channels are found throughout the cardiovascular system and skeletal muscle and couple cellular metabolism to excitability. AIMS individuals show fatigability, muscle spasms, and cardiac dysfunction. We found reduced exercise performance in mouse models of AIMS harboring premature stop codons in ABCC9. Given the roles of K_ATP channels in all muscles, we sought to determine how myopathy arises using tissue-selective suppression of K_ATP and found that LoF in skeletal muscle, specifically, underlies myopathy. In isolated muscle, SUR2 LoF res

SUBMITTER: McClenaghan C 

PROVIDER: S-EPMC10245035 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature