Mitochondrial-Mediated Oxidative Ca²⁺/Calmodulin-Dependent Kinase II Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An In Silico Study.

ABSTRACT: Background Oxidative stress-mediated Ca²⁺/calmodulin-dependent protein kinase II (Ca MKII) phosphorylation of cardiac ion channels has emerged as a critical contributor to arrhythmogenesis in cardiac pathology. However, the link between mitochondrial-derived reactive oxygen species (md ROS ) and increased Ca MKII activity in the context of cardiac arrhythmias has not been fully elucidated and is difficult to establish experimentally. Methods and Results We hypothesize that pathological md ROS can cause erratic action potentials through the oxidation-dependent Ca MKII activation pathway. We further propose that Ca MKII -dependent phosphorylation of sarcolemmal slow Na⁺ channels alone is sufficient to elicit early afterdepolarizations. To test the hypotheses, we expande

SUBMITTER: Yang R 

PROVIDER: S-EPMC6201444 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature