Hyperglycemia regulates cardiac K⁺ channels via O-GlcNAc-CaMKII and NOX2-ROS-PKC pathways.

ABSTRACT: Chronic hyperglycemia and diabetes lead to impaired cardiac repolarization, K⁺ channel remodeling and increased arrhythmia risk. However, the exact signaling mechanism by which diabetic hyperglycemia regulates cardiac K⁺ channels remains elusive. Here, we show that acute hyperglycemia increases inward rectifier K⁺ current (I_K1), but reduces the amplitude and inactivation recovery time of the transient outward K⁺ current (I_to) in mouse, rat, and rabbit myocytes. These changes were all critically dependent on intracellular O-GlcNAcylation. Additionally, I_K1 amplitude and I_to recovery effects (but not I_to amplitude) were prevented by the Ca²⁺/calmodulin-dependent kinase II (CaMKII) in

SUBMITTER: Hegyi B 

PROVIDER: S-EPMC8349245 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature