Hypoxia inhibits the cardiac I _K1 current through SUMO targeting Kir2.1 activation by PIP₂.

ABSTRACT: Cardiovascular diseases remain the leading cause of death worldwide. Most deaths are sudden and occur secondary to the occlusion of coronary arteries resulting in a rapid decrease in cellular oxygen levels. Acute hypoxia is proarrhythmic, leading to disordered electrical signals, conduction block, and uncoordinated beating of the myocardium. Although acute hypoxia is recognized to perturb the electrophysiology of heart muscle, the mechanistic basis for the effect has remained elusive, hampering the development of targeted therapeutic interventions. Here, we show that acute hypoxia activates the redox-sensitive SUMO pathway in cardiomyocytes, causing rapid inhibition of the inward-rectifying K⁺ channel, Kir2.1. We find that SUMOylation decreases the activation of Kir2.1 channels

SUBMITTER: Xu Y 

PROVIDER: S-EPMC9437851 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature